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BACTERIOLOGICAL  AND  CLINICAL  STUDIES 


OF    THE 


DIARRHEAL   DISEASES    OF    INFANCY 


FROM 


THE  ROCKEFELLER  INSTITUTE  FOR  MEDICAL  RESEARCH 


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BACTERIOLOGICAL  AND    CLINICAL  STUDIES 


OF    THE 


DIARRHEAL    DISEASES    OF    INFANCY 


WITH   REFERENCE   TO   THE 


BACILLUS   DYSENTERIC  (Shiga) 


FROM 


THE     ROCKEFELLER     INSTITUTE     FOR    MEDICAL     RESEARCH 


Edited  by 
SIMON     FLEXNER,    M.D. 

AND 

L.    EMMETT     HOLT,    M.D 


1904 


im 


New  York 

Rooney  &  Otten  Printing  Co. 

114-120  West  30TH  St. 


CONTENTS. 


INVESTIGATION    OF    1 902. 

Bacteriological  Report.     By  C.  W.  Duval  and  V.  H.  Bassett 7 

Clinical  Report.     By  J.   H.   Mason  Knox 26 


INVESTIGATION    OF    I9O3. 

Introduction.     By  Simon  Flexner   31 

Bacteriological  Report.     By  C.  W.  Duval  and  E.  H.  Shorer 42 

By   Martha   Wollstein   and   Grace  Dewey 55 

By  Frederick  P.   Gay  and  E.   McD.   Stanton 61 

By  Louise  Cordes   •  •  •  •  67 

By  W.  W.  Waite    72 

By  Arthur  I.   Kendall 76 

By   Paul   A.   Lewis    82 

By  Victor  H.  Bassett  88 

Pathological   Report.     By  John   Howland    94 

Report  on  Blood  Reactions.     By  Chas.  K  Whine 118 

Bacteriological  and  Pathological  Conclusions.     By  Simon  Flexner 121 

Clinical  Report.     By  L.  E.  La  Fetra  and  John  Howland 137 

By  J.  H.   Mason   Knox 148 

By   Louise   Cordes    155 

By  Samuel  Amberg   159 

By  Rowland  G.  Freeman 163 

By  Louis  M.  Warfield   166 

By  Robert  W.   Hastings    17° 

By  Dorothy  M.  Reed 175 

Clinical  Conclusions.     By  L.  Emmett  Holt  185 

Dysentery   Bacillus    in    Relation   to   the    Normal    Intestines    of   Infants.      By 

Martha   Wollstein    193 


PREFATORY    NOTE. 

It  was  originally  intended  to  include  in  this  monograph  only  the 
papers  relating  to  the  work  of  the  summer  of  1903. 

For  the  sake  of  completeness,  however,  it  has  seemed  best  to  intro- 
duce also  the  papers  of  Duval  and  Bassett  and  of  Knox  covering  ob- 
servations made  in  the  summer  of  1902.  The  paper  of  Duval  and 
Bassett  has  previously  appeared  only  in  abstract. 

There  has  been  added  also  the  report  of  the  observations  of  Woll- 
stein  upon  the  "Occurrence  of  the  Bacillus  Dysenteriae  in  Normal  In- 
fants." This  work  was  undertaken  subsequent  to  the  findings  of  the 
summer  of   1903. 

The  Editors. 


THE   ETIOLOGY   OF    SUMMER   DIARRHEA   IN    INFANTS. 

(investigation  of  1902.) 

BY    CHARLES    W.    DUVAL   AND    VICTOR    H.    BASSETT. 

From  the  Laboratory  of  the  Thomas  Wilson  Sanitarium,   Baltimore.* 

The  successful  studies  of  Japanese  dysentery  by  Shiga  in  1898,  which 
led  to  the  isolation  of  B.  dysenteriae  and  its  demonstration  as  the  cause 
of  acute  endemic  dysentery  were  followed  by  the  studies  of  acute  tropi- 
cal dysentery  in  Manila  by  Flexner1  in  1900  and  epidemic  dysentery  in 
Germany  by  Kruse2  in  1901  with  results  confirming  the  observations 
of  Shiga.  Since  that  time  a  considerable  number  of  observations  bear- 
ing upon  and  extending  the  studies  just  mentioned  have  been  carried 
out  both  in  the  United  States  and  elsewhere.  Inasmuch  as  the  or- 
ganism has  also  been  obtained  from  cases  of  dysentery  in  troops  re- 
turning from  China,4  in  Constantinople,5  in  Italy6  and  other  European 
countries,7  its  wide  diffusion  in  nature  as  well  as  its  pathogenicity  are 
clearly  evident. 

*[A  brief  preliminary  report  of  the  results  of  this  investigation  was  pub- 
lished in  American  Medicine,  September  13,  1902,  Vol.  IV,  p.  417.  The  present 
article  and  the  following  one  by  Dr.  Knox,  which  contain  the  full  reports,  were 
ready  for  publication  in  October,  1902,  and  are  here  published  in  their  original 
form.  In  consequence  of  the  unfortunate  delay  in  publication  for  which  the 
authors  are  not  responsible,  later  articles  upon  the  same  subject  have  been  pub- 
lished without  full  knowledge  of  the  detailed  results  obtained  by  Messrs.  (now 
Drs.)  Duval  and  Bassett  in  the  summer  of  1902,  whose  investigations  at  that 
time  were  the  first  to  demonstrate  an  etiological  relationship  between  the  bacillus 
of  dysentery  and  infantile  summer  diarrhea,  and  will  remain  of  fundamental 
importance. — Wm.   H.   Welch.] 

1.  The  Johns   Hopkins   Bulletin,   February,    1900. 

2.  Deutsche  med.  Wochnschr.,  1901,  XXVII,  370. 

3.  Loc.  cit. 

4.  Pfuhl,  Veroffentlichungen  auf  dem  Gebiete  des  Militar-Sanitatswesens, 
1902,   65. 

5.  Deycke,  Deutsche  med.  Wchnschr.,  1901,  XXVII,  10. 

6.  Celli.     Personal  communication  and  culture  sent. 

7.  Th.  Muller,  Centralblatt  fur  Bakteriol.  u.  Parasitenkunde,  1902,  XXXI,  558. 
Rosenthal,  Deutsche  med.  Wchnschr.,  1903,  XXIX,  97. 


8  Charles  IV.  Duval  and  Victor H.  Bassett. 

That  the  summer  diarrheas  of  infants  have  an  infectious  origin  has 
long  been  believed  by  clinicians  and  pathologists.  Indeed,  within  the 
last  ten  or  fifteen  years  notable  contributions  to  the  bacteriology  of 
the  dejecta,  intestinal  contents,  and  intestinal  mucosa  in  the  disease 
have  been  made  by  Escherich  and  his  pupils  in  Germany  and  by  Booker 
in  this  country.  The  valuable  studies  of  these  investigators  have  been 
less  conclusive  than  might  have  been  expected  by  reason  of  the  multi- 
plicitv  of  bacteria  in  the  intestine  and  the  absence  of  satisfactory  cri- 
teria of  distinction  between  the  saprophytic  and  parasitic  varieties. 
Notwithstanding  these  drawbacks  some  facts  have  been  established. 
But  no  success  has  attended  the  efforts  to  prove  the  action  of  a  specific 
organism  as  the  cause  of  infantile  summer  diarrheas.  Indeed,  no  patho- 
genic organism  was  constantly  present  in  the  discharges. 

The  nomenclature  of  summer  diarrhea  is  by  no  means  clear.  The 
various  names  given  and  the  divergent  views  held  as  to  its  nature  well 
illustrate  the  confusion  that  purely  symptomatic  and  anatomical  con- 
ceptions bring  into  the  classification  of  disease. 

The  original  problem  set  before  us  the  past  summer  (1902),  was  the 
investigation  of  the  intestinal  bacteria  of  infants  suffering  from  differ- 
ent forms  of  summer  diarrhea,  especially  as  to  the  presence  of  the  Ba- 
cillus dysenteriae  (Shiga).  Subsequently,  as  a  control,  the  stools  of 
healthy  infants  were  also  studied.  Following  the  method  of  investiga- 
tion employed  by  Shiga  in  adult  dysentery  it  was  our  intention  to  make 
use  of  the  agglutination  reaction  of  the  blood  of  the  patients  with  the 
organisms,  in  isolating  the  pathogenic  organisms  from  the  dejecta. 
Prof.  Flexner  drew  our  attention  to  this  method  of  approaching  the 
problem,  and  suggested  the  lines  of  special  study. 

The  present  unsatisfactory  state  of  our  knowledge  of  the  etiology  of 
the  intestinal  inflammations  of  children  may  be  gathered  from  the  state- 
ments regarding  it  to  be  found  in  any  of  the  recent  authoritative  text- 
books upon  the  diseases  of  children. 

Methods  of  Studying  the  Dejecta, — On  account  of  the  admixture  of 
microorganisms  and  the  great  capacity  for  multiplication  in  the  in- 
testinal contents  of  the  colon  bacilli,  special  methods  should  be  resorted 
to  in  order  to  separate  specific  foreign  microorganisms.  The  procedure 
employed  by  us  in  isolating  B.  dysenteriae  from  the  stools  was  essen- 
tially that  described  by  Vedder  and  Duval.1  The  stool  is  collected  pref- 
erably upon  a  sterile  gauze  pad  that  is  placed,  in  the  usual  manner,  over 
the  buttocks,  previously  cleansed  with  bichloride,  etc.,  and  over  this 

'Vedder  and  Duval :    The  Journal  of  Experimental  Medicine,  1902,  vi,  181. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  9 

the  napkin  is  bound.  The  rectal  tube  may  be  employed,  but  it  presents 
no  special  advantages  over  the  former  method.  The  stool  should  be 
examined  immediately,  if  possible,  and  always  without  unavoidable 
delay,  if  successful  and  trustworthy  bacteriological  results  are  to  be 
obtained. 

Experience  has  taught  that  stools  containing  blood  and  mucus  are 
especially  favorable  for  isolating  the  bacillus  of  dysentery.  One 
chooses  by  preference  the  bloody  material  which  is  suspended  in  sterile 
broth  in  quantity  sufficient  to  give  it  a  turbid  appearance.  As  a  rule 
about  six  loopfuls  (oese)  are  used,  and  if  several  blood-flecked  spots 
occur  some  is  taken  from  each.  When  dealing  with  mucus  rather  than 
blood  the  same  course  is  pursued,  although  sometimes  three  loopfuls 
suffice  to  render  the  bouillon  (about  10  c.c.)  cloudy.  When  bloody 
and  mucous  specks  are  distinguishable  in  the  same  stool  one  plates  from 
each  separately. 

The  number  of  plates  prepared  depends  upon  the  character  of  the 
stool — whether  fecal,  mucous,  or  bloody.  A  large  series  of  plates  is 
prepared  from  muco-fecal  matter  and  a  smaller  number  from  material 
containing  much  blood.  The  number  of  plates  prepared  from  the  dif- 
ferent dejecta  varied  from  18  to  30.  Of  this  series  plates  Xo.  1  and 
No.  4  were  usually  of  little  use,  the  first  because  of  too  heavy,  the 
last  of  too  light  seeding.  What  is  aimed  at  is  to  secure  a  large  num- 
ber of  plates  of  Nos.  2  and  3,  for  subsequent  study. 

The  dilutions  are  made  in  the  usual  way,  after  the  settling  of  the 
coarser  particles,  by  carrying  2,  4,  6,  or  8  loopfuls  of  the  suspension, 
depending  upon  its  opacity,  into  a  second  bouillon  tube  (corresponding 
to  agar  plate  Xo.  1  which  is  discarded)  and  from  this  bouillon  into 
the  melted  agar  tubes  (2,  4,  or  6)  using  in  each  the  same  number  of 
loopfuls  usually  six  (these  forming  plates  Xo.  2)  and  from  these  the 
same  number  of  loopfuls  of  agar  suspension  .Xo.  2  are  carried  into  Xo. 
3  tubes  (also  2,  4,  or  6).  A  variation  of  this  method  of  seeding,  which 
insures  a  more  certain  distribution,  is  to  carry  about  two  loopfuls  into 
one  tube  of  agar,  four  into  another,  six  into  another,  etc.  What  may  be 
regarded  as  successful  plates  are  those  presenting  about  25  to  200  super- 
ficial colonies.  Thinly  seeded  plates,  namely  Xo.  4  plates,  in  all  except 
very  favorable  and  acute  cases  usually  show  only  B.  coli. 

The  most  favorable  material  from  which  to  isolate  B  Jysenteriae  is 
obtained  at  autopsy,  after  opening  the  lower  intestine  with  sterile  in- 
struments, by  scraping  the  mucous  membrane  with  a  sterile  knife ;  the 
scrapings  being  introduced  into  bouillon  and  used  for  plating  as  above 
described.    We  shall  have  occasion  later  to  dwell  upon  the  significance 


io  Charles  W.  Duval  and  Victor  H.  Bassett. 

of  the  fact  that  this  organism  is  more  abundant  in  the  substance  of  the 
mucous  membrane  than  in  the  intestinal  contents,  and  is  in  far  less 
danger  of  being  overgrown  post  mortem  in  that  location  than  in  the 
dejecta. 

The  plates  having  been  reversed,  to  avoid  condensation  upon  the 
surface  of  the  agar,  are  permitted  to  incubate  at  t,7°  C.  for  twenty- 
four  hours.  The  first  crop  of  colonies  thus  obtained  having  been 
marked  off  with  a  blue  wax  pencil,  as  described  by  Vedder  and  Duval, 
the  plates  are  returned  to  the  incubator  for  another  twenty-four  hours. 
This  second  crop  of  colonies  is  now  examined  and  those  presenting 
the  characters  of  B.  dysenterice  {vide  infra)  are  transplanted  to  glucose- 
agar.  Incubation  over  night  will  suffice  to  separate  all  gas-forming 
from  non-gas-forming  varieties.  Among  the  latter  B.  dysenterice  is  to 
be  sought.  While  a  certain  number  of  dysentery  colonies  will  appear 
within  the  first  twenty-four  hours  the  majority  grow  more  slowly  than 
those  of  B.  coll.  This  fact  is  further  emphasized  by  the  occasional 
appearance  of  the  former  colonies  as  late  as  the  fourth  day  of  incu- 
bation of  the  plates.  In  some  instances  with  positive  blood  reactions, 
in  which  colonies  developing  late  were  few  in  number  and  non-dysen- 
teric m  type,  examination  after  some  days  of  the  plates  marked  off  on 
the  first  day  has  yielded  characteristic  colonies,  in  small  number,  of  the 
dysentery  bacillus. 

Physical  Characteristics  of  Colonies  of  B.  dysenterice  on  Agar-agar. 
— Inasmuch  as  no  small  part  of  the  success  of  isolation  of  the  bacillus 
of  dysentery  from  stools,  etc.  depends  upon  the  recognition  of  the 
colony  and  since  agar-agar  suffices  for  this  distinction  and  possesses 
the  important  advantage  of  permitting  rapid  cultivation,  a  somewhat 
detailed  description  of  the  typical  colonies  upon  this  medium  is  given. 
The  general  cultural  characters  of  the  bacillus  will  not  be  described  as 
this  has  already  been  done  by  Flexner1  and  by  Vedder  and  Duval.2 

We  also  noted  that  the  reaction  of  the  nutrient  agar-agar  is  of  prime 
importance ;  it  should  be  distinctly  acid  to  litmus.  Should  the  reaction 
be  neutral  to  litmus  the  difficulty  of  isolation  of  B.  dysenterice  is  very 
much  increased ;  and  in  the  presence  of  an  alkaline  reaction  isolation 
is  rendered  almost  impossible.  The  reaction  influences  rapidity  of 
growth,  and  perhaps,  also,  the  type  of  colony.  Alkalinity  is  a  definitely 
inhibitory  condition. 

'Flexner:  On  the  Etiology  of  Tropical  Dysentery,  Philadelphia  Medical 
Journal,  igoi,  vi,  414;  A  Comparative  Study  of  Dysenteric  Bacilli,  Univ.  of 
Penna.  Med.  Bulletin,  1901,  xiv,  190. 

2Loc.  cit. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  11 

When  grown  upon  the  acid  medium  the  forms  of  the  superficial 
colonies,  which  in  age  are  not  younger  than  24  or  older  than  48  hours, 
are  so  distinctive  that  they  can  be  recognized  with  much  confidence. 
To  this  end  the  plates  should  be  thinly  spread  and  the  layer  of  medium 
such  as  to  insure  a  large  proportion  of  superficial  colonies. 

With  the  naked  eye  the  24-hour  colonies  average  1  mm.  in  diameter 
and  within  the  next  12  hours  they  add  0.5  mm.  to  their  width.  The 
48-hour  colony  is  about  2  mm.  in  diameter.  At  the  expiration  of  24 
hours  a  well-defined  nucleus  can  be  detected,  which  remains  stationary 
during  the  next  12  to  24  hours.  The  margin  of  the  colony  is  uniform, 
regular,  and  unbroken,  and  gradually  merges  into  the  medium.  The 
colony  of  36  hours'  growth  shows  already  the  zonular  striation  upon 
which  we  lay  much  stress,  and  this  appearance  persists  almost  or  quite 
unchanged  up  to  about  48  hours.  The  consistence  varies  with  the  age 
of  the  colony  :  at  24  hours  the  colonies  are  delicate  and  semi-transluc- 
ent ;  at  48  hours  they  are  more  opaque,  but  still  of  considerable  delicacy. 

The  former  are  bluish-white  in  colo1",  the  latter  whiter,  but  even  when 
viewed  by  reflected  light  do  not  exhibit  a  yellowish  tint.  The  surface 
is  not  elevated  perceptibly  above  the  medium  and  the  reflection  is  dull. 

Lnder  a  magnification  of  ten  times,  the  triple  zone  is  strikingly 
evident.  The  nucleus  of  the  24-hour  colony  is  regular  in  outline  and 
unbroken,  the  granules  of  the  middle  zone  are  regular  in  size  and  ap- 
pearance and  equidistant  from  one  another.  At  about  36  hours  the 
nucleus  begins  to  show  irregularities ;  the  periphery  presents  nodosities 
which  a  little  later  (48  hours)  become  separated  and  migrate  towards 
the  middle  zone.  The  margin  which  is  regular  up  to  36  hours  begins 
now  to  assume  a  wavy  outline  which  is  persistent.  The  color  is  bluish 
by  transmitted  and  brownish  by  reflected  light. 

Colonies  older  than  48  hours  cannot  be  regarded  as  readilv  distin- 
guishable from  those  of  B.  coli.  After  this  period,  the  growth  in  thick- 
ness and  opacity  as  well  as  in  superficies  entirely  obliterates  the  charac- 
ters upon  which  differentiation  from  B.  coli  can  be  made.  As  com- 
pared with  colonies  of  the  dysentery  bacillus  of  24  to  48  hours'  growth, 
those  of  the  colon  bacillus  of  corresponding  ages  are  larger,  thicker, 
elevated,  more  opaque,  and  of  yellowish  hue.  A  nucleus  is  inconstant 
and  the  zonular  striation  wanting. 

Record  of  Cases. — At  the  present  time  and,  indeed,  until  such  time 
as  the  etiology  of  the  summer  diarrheas  is  definitely  established,  it  is 
desirable  to  combine  the  description  of  the  bacteriological  findings  with 
certain  important  facts  in  the  clinical  history  of  the  cases  studied.  For 
this  reason  we  present  here  a  brief  report  of  the  dejecta  of  the  cases 


12  Charles  W.  Duval  and  Victor  H.  Bassett. 

examined ;  further  reference  to  the  clinical  data  will  be  found  in  the 
report  of  Dr.  Knox. 

Case  I. — Irving.  Infection  occurred  in  the  Sanitarium.  First  stool  examined 
bacteriologically  was  semi-liquid,  muco-fecal  in  character.  Later  specimen  con- 
sisted almost  wholly  of  mucus,  necked  here  and  there  with  blood;  still  later 
there  was  muco-pus.  Coverslips  showed,  besides  leucocytes  and  red  corpuscles, 
many  bacilli  of  colon  morphology  and  some  cocci.  Of  26  colonies  transplanted 
to  glucose-agar  five  developed  no  gas  and  proved  later  to  be  B.  dysenteries. 

Case  II. — Williams.  Movement  semi-solid,  muco-fecal.  No  blood  or  pus. 
Isolation  of  B.  dysenteries  positive.  A  second  plating  from  this  case  gave  iden- 
tical results. 

Case  III. — Schuster.  Stool  semi-liquid,  bloody,  and  muco-purulent.  Result 
positive. 

Case  IV. — Schultz.  Semi-solid,  mucous  stool ;  no  blood  or  pus.  B.  dysen- 
teries obtained  in  small  numbers  after  several  trials. 

Case  V. — Riall.  Stool  muco-fecal,  greenish-brown  in  color.  First  trial  nega- 
tive. A  few  days  later  a  small  quantity  of  bloody  mucus  appeared  in  the  stool ; 
result  positive.  One  week  later  a  large  mucous  stool  containing  some  firm  white 
clumps  and  mucus  streaked  with  blood  was  obtained.  Separate  suspensions  into 
bouillon  were  made  from  the  blood-stained  and  blood-free  thin  mucous  flecks. 
From  the  former  30  colonies,  from  the  latter  two  colonies  of  B.  dysenteries  were 
secured. 

This  case  is  of  interest  as  illustrating  the  difficulties  attending  the  study  of 
the  dejecta  and  as  emphasizing  the  necessity  for  repeated  examination  before 
deciding  upon  a  negative  result.  The  first  examination  gave  no  dysentery  ba- 
cilli, the  second  gave  many,  the  third  few,  and  the  fourth  none,  all  within  a 
period  of  ten  days. 

Case  VI. — Wolf.  Semi-liquid,  yellowish-brown,  mucous  stool ;  here  and  there 
small  flecks  of  blood.     Positive  result;    few  colonies. 

Case  VII. — Friedman.  Specimen  contained  much  mucus  and  a  few  streaks 
of  blood  intermingled  with  fecal  matter.  Of  30  colonies  subcultured  into  glu- 
cose-agar, nine  gave  B.  dysenteries.  Second  specimen :  very  bloody  mucous  stool. 
Of  40  subcultured  tubes,  37  consisted  of  B.  dysenteries. 

Case  Villi — Silk.  First  stool  semi-solid  and  mucous ;  no  blood.  Very  few 
dysentery  colonies  obtained.  Second  specimen  contained  muco-bloody  patches ; 
a  large  number  of  colonies  were  secured.  The  blood  of  this  case  agglutinated 
powerfully  and  retained  this  capacity  for  more  than  eight  weeks  {vide  infra). 

Case  IX. — Hoffman.  Small,  liquid,  non-fecal  stool  containing  much  bloody 
mucus  and  pus.  From  this  material  a  high  percentage  of  the  organisms  was  ob- 
tained. A  second  stool  was  fecal  with  only  a  trace  of  mucus ;  no  result.  One 
week  later  blood  again  appeared  in  the  stool  when  B.  dysenteries  was  obtained 
from  the  plates  prepared  from  the  bloody  but  not  from  the  purely  mucous  ma- 
terial. In  this  last  examination  ten  new  colonies  appeared  on  the  48-hour  plates, 
all  of  which  proved  to  be  B.  dysenteries. 

Case  X. — Rabinowitz.  First  specimen  small,  containing  viscid,  greenish  mu- 
cous lumps  and  purulent  matter  flecked  with  blood.  Twenty-four  hours  later 
the  stool  was  fecal  and  mucous.  Two  days  later  blood  again  appeared.  In  the 
first  specimen  dysentery  bacilli  were  abundant ;    in  the  second,  they  were  not 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  13 

found ;  streptococci  were  present.  This  was  a  fatal  case ;  autopsy  not  per- 
mitted. A  rectal  tube  was,  however,  inserted  and  the  mucosa  of  the  colon 
scraped;    from  the  scrapings  B.  dysenteries  was  obtained. 

Case  XI. — Pursley.  Large,  muco-fecal  stool  containing  pus.  Result  positive; 
small  number  of  colonies  of  B.  dysenteries  isolated. 

Case  XII. — Stevens.  Semi-solid,  muco-fecal  specimen.  Few  colonies  of  dys- 
entery bacillus ;  streptococci  in  moderate  numbers'.  Two  weeks  later  bloody 
streaks  were  observed  on  the  napkin.  From  the  bloody  mucus  a  large  number 
of  colonies  of  B.  dysenteries  were  obtained.  This  case  terminated  fatally  and 
an  autopsy  was  performed  by  Dr.  Flexner.  An  abstract  of  the  protocol,  so  far 
as  it  relates  to  the  intestines,  is  as  follows  :  The  intestines  are  moderately  dis- 
tended and  the  large  intestine  is  dilated  and  thickened.  On  opening  the  large 
intestine  the  entire  colon  is  distended  and  the  mucous  membrane  is  thickened 
and  covered  with  bloody  mucus.  Numerous  punctiform  hemorrhages  and  small 
ulcers  extending  through  the  mucosa  are  present  in  the  large  intestine,  while  the 
small  intestine  contains  muco-sanguinolent  contents,  the  mucosa  showing  puncti- 
form hemorrhages  but  no  ulcerations.  The  injected  and  hemorrhagic  condition 
of  the  small  intestine  disappears  at  about  the  upper  third  of  the  jejunum. 

Cultures  gave  B.  dysenteries  from  the  intestine,  mesenteric  glands,  and  liver. 
The  greatest  number  of  colonies  was  obtained  from  the  scrapings  of  the  mucous 
membrane ;  the  next  greatest  number  from  the  substance  of  the  mesenteric  gland 
of  which  a  large  part  was  transplanted. 

Case  XIII. — Mortensen.  Semi-solid,  greenish-yellow  mucous  specimen  with 
little  fecal  matter  and  blood.     Positive  for  B.  dysenteries. 

Case  XIV. — Pittle.  Abundant  fluid  stool  with  little  fecal  matter  and  some 
mucus ;    no  blood.     Small  number  of  dysentery  bacilli  obtained. 

Case  XV. — Hicky.  Small,  thick,  greenish,  mucous  stool  containing  blood  and 
pus.     Large  number  of  colonies  of  B.  dysenteries. 

'  Case  XVI.- — Carr.  Stool  consisted  almost  entirely  of  pus  and  mucus  with 
much  blood.  Regarded  as  a  highly  favorable  specimen.  Result  positive.  This 
case  came  to  autopsy  and  the  material  obtained  by  scraping  the  mucosa  yielded 
a  much  larger  percentage  of  colonies  of  B.  dysenteries.  No  streptococci  were 
found. 

Case  XVII. — Lutz.  First  specimen  dark,  semi-liquid,  containing  mucus  but 
no  blood.  One  colony  of  B.  dysenteriae  secured.  Second  and  third  specimens 
(one  week  later)  contained  mucus  and  blood.  From  the  third  a  number  of  col- 
onies were  obtained ;  streptococci  present.  Fourth  specimen  contained  much 
blood ;  a  large  number  of  positive  colonies  secured.  Sixth  specimen  :  abundant 
muco-pus  with  little  blood ;  positive  but  a  smaller  number  of  colonies  of  the 
dysentery  bacillus  found  than  in  preceding   specimen. 

Case  XVIII. — Heiland.  Mucous  stool  with  a  little  blood  and  fecal  matter. 
Second  stool  almost  wholly  mucus  and  blood.     Positive  for  B.  dysenteries. 

Case  XIX. — Speckerman.  Semi-solid,  muco-fecal  stool ;  no  blood.  Result 
positive  for  B.  dysenteriae.  The  urine  from  the  child  was  albuminous  and  cloudy; 
a  bacilluria  existed  which  was  due  to  B.  coli.  A  painstaking  attempt  to  find  B. 
dysenteries  in  the  urine  failed.  The  child  died  and  the  large  intestine  at  autopsy 
showed  enlargement  of  the  solitary  follicles  with  pitting  of  their  centres  and 
surrounding  deep  congestion ;  no  definite  ulceration  was  present.  Scrapings 
from  the  mucosa  gave  a  high  percentage  of  colonies  of  B.  dysenteries. 


14  Charles  W.  Duval  and  Victor  H.  Bassett. 

Case  XX. — Lavine.  Abundant,  greenish,  mucous  stool ;  no  fecal  matter. 
Small  number  of  colonies  of  dysentery  bacillus. 

Case  XXI. — Love.  Thick,  yellowish-green  stool  showing  blood-stained  mucus. 
From  the  plates  B.  coli,  B.  proteus  and  B.  dysenteric?  isolated.  All  tested  with 
patient's  blood  and  only  the  last  reacted  positively. 

Case  XXII. — Proser.  The  specimen  examined  consisted  of  a  muco-fecal  stool 
containing  a  few  flecks  of  blood.  The  result  was  positive.  This  child  died  later, 
but  an  autopsy  was  not  permitted.  However,  by  passing  the  rectal  tube  and 
scraping  the  mucosa  a  small  quantity  of  blood-stained  material  was  secured 
from  which  B.  dysenteries  was  obtained. 

Case  XXIII. — Walsh.  In  the  abundant  mucous  stool  a  few  small  collections 
of  pus  cells  occurred ;  result  positive.  Some  twelve  days  later  a  second  exami- 
nation of  a  semi-fluid,  muco-fecal  stool  was  made  with  negative  results.  The 
child  died  five  days  after  the  second  examination  and  an  autopsy  was  made  eight 
hours  after  death.  The  lymphatic  nodes  of  the  cecum  were  swollen  and  the 
mucosa  over  them  pitted ;  the  mucosa  of  the  transverse  eclon  showed  numerous 
small,  round  ulcers  occurring  as  pits  in  the  enlarged  solitary  nodes  ;  the  mucosa 
of  the  descending  colon  was  thickened  but  intact.  The  contents  of  the  large 
intestine  were  muco-pus,  blood  being  absent. 

The  bacteriological  examination  gave  B.  coli,  B.  lactis  acrogenes.  Strepto- 
coccus pyogenes,  and  B.  dysenteric  ;  the  last  was  obtained  from  the  intestine 
only;  the  others  from  additional  organs,  such  as  the  liver  and  mesenteric  glands. 
This  case  was  instructive  in  that  on  some  of  the  plates  B.  dysenteric  came  out 
very  late. 

Case  XXII '. — O'Donnell.  The  specimen  examined  had  a  bad  odcr,  consisted 
chiefly  of  feces  and  mucus  and  showed  a  few  patches  of  blood-stained  mucus. 
Using  the  bloody  areas  ten  of  the  twelve  transplantations  to  glucose  agar  proved 
to  be  B.  dysenterice.  The  next  stool  contained  mere  blood ;  27  out  of  28  trans- 
plants were   dysentery  bacilli. 

Case  XXV. — Rea.  Stool  muco-fecal;  no  blood.  Eight  of  30  tubes  trans- 
planted positive  for  B.  dysenterice.  It  is  to  be  noted  that  the  blood  in  this  case 
failed  to  give  the  agglutination  test,  although  tried  several  times. 

Case  XX]' I. — Tucker.  Small  greenish,  purulent,  blood-flecked  stool.  Sev- 
eral examinations  were  required  to  discover  the  organism,  which  was  finally 
found  in  very  small  numbers. 

Case  XXI 'II. — Golman.  The  first  stool  was  chiefly  fecal;  very  few  dysentery 
bacilli.  The  second  stool  examined  three  days  later  was  muco-purulent  and  con- 
tained blood.  Many  dysentery  bacilli  found.  A  third  stool  gave  good  results. 
The  child  died  and  an  autopsy  was  refused.  The  mucosa  of  the  lower  gut  was 
curetted  and  from  this  material  many  colonies  of  B.  dysenterice  developed.  The 
plates  in  this  case  contained  many  colonies  of  a  bacillus  which  agreed  culturally 
with  B.  pyocyaneus. 

Case  XXVIII. — Stevens.  Stools  contained  mucus,  but  little  blood.  Results 
were  positive  in  26  of  the  37  glucose-agar  tubes  inoculated. 

Case  XXIX. — Macomber.  Specimen  abundant,  greenish,  showing  mucus  and 
some  purulent  foci  and  bloody  mottling.  Results  positive  for  dysentery  bacilli 
which  were  present  in  large  numbers. 

Case  XXX. — Gerhardt.  Muco-fecal  stool  without  blood.  Of  36  colonies 
transplanted,   14  proved  to  be  B.  dysenteric 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  i  5 

Case  XXXI. — Lubinsky.  Semi-solid  fecal  stool  with  a  foul  odor.  No  blood 
present.  Of  a  large  series  of  transplantations  to  glucose-agar  three  tubes  of 
B.  dysenteric?  were  recovered. 

Case  XXXII. — Jackson.  Very  small  mucous  stool  containing  no  blood  and 
little  fecal  matter.     A  small  number  of  dysentery  bacilli   were  recovered. 

Case  XXXIII. — Hoffman.  Stool  large,  muco-purulent  and  blood-stained. 
B.  dysenteric?  present. 

Case  XXXIV. — Hirste.  Muco-fecal  stool ;  no  blood.  Small  number  of  col- 
onies of  dysentery  bacillus. 

.    Case  XXXVI. — Plater.     Specimen  muco-fecal  with  few  spots  of  blood.     Of 
49  subcultures  30  were  B.  dysenteric?. 

Case  XXXVII. — Dukehardt.  This  case  is  given  in  some  detail  in  order  to 
show  the  difficulties  that  sometimes  attend  the  isolation  of  B.  dysenteric?.  The 
first  stools  examined  were  scanty,  viscid,  whitish,  and  contained  mucus ;  blood 
was  absent.  From  two  stools  eight  plates  were  made.  A  small  number  of  new 
colonies  developed  on  the  second  day.  These  were  streptococci.  Seventy  sub- 
cultures were  made  from  the  new  and  from  suspicious  looking  old  colonies.  The 
bacillus  of  dysentery  was  not  obtained ;  the  organisms  transplanted  were  strep- 
tococci, B.  coli,  and  an  undetermined  bacillus  which  failed  to  react  to  the  serum 
of  the  patient.  Five  days  later  cultures  were  taken  from  some  slightly  bloody 
mucus  obtained  by  gently  scraping  the  rectal  mucosa  through  a  proctoscope.  Of 
100  colonies  subcultured  only  four  proved  to  be  B.  dysenteric?,  the  rest  consist- 
ing of  streptococci  and  B.  coli. 

Case  XXXVIII. — Bogatsky.  Muco-fecal  stool ;  no  blood.  Small  number  of 
colonies  of  B.  dysenteric?  developed. 

Case  XXXIX. — Triebosky.  No  stool  was  obtained  from  this  case ;  but 
scrapings  from  the  intestinal  mucosa  gave  a  small  number  of  colonies  of  B.  dys- 
enteric?. 

Case  XL. — Stabler.  Scanty,  liquid,  muco-fecal  stool ;  no  blood.  The  plates 
from  this  case  contained  streptococci  in  predominating  numbers  ;  the  bacillus  of 
dysentery  was  recovered  in  small  numbers  only. 

Case  XLI. — Out-patient.  Stool  secured  with  rectal  tube.  The  specimen  was 
dark  green  and  liquid;  no  blood  or  mucus.  Twenty  plates  were  made;  of  these 
one  is  worthy  of  special  description  since  at  the  end  of  twenty-four  hours  only 
seven  colonies  had  appeared.  These  were  marked  and  later  determined  to  con- 
sist of  B.  coli.  Upon  examining  this  plate  24  hours  later  over  200  new  super- 
ficial colonics  had  appeared.     All  these  proved  to  be  B.  dysenteriae. 

Case  XLII. — Out-patient.  The  blood  of  this  patient  had  been  tested  in  ad- 
vance with  positive  results  on  the  fifth  day  of  the  disease.  Stool  obtained  with 
the  rectal  tube  consisted  chiefly  of  mucus  with  here  and  there  bloody  flecks ; 
a  moderate  number  of  B.  dysenteric?  present. 

The  foregoing  list  comprises  the  records  of  42  cases  of  infantile 
diarrhea  in  which  the  bacillus  of  dysentery  was  found.  The  total 
number  of  cases  examined  for  dysentery  bacilli  was  53 ;  in  11  cases 
negative  results  were  obtained  although  in  all  the  fresh  stools  were 
studied.  Of  the  11  negative  cases,  2  were  fatal  but  autopsies  could 
not  be  secured ;  in  3  cases  a  definite  history  of  entero-colitis  of  some 


1 6  Charles  W.  Duval  and  Victor  H.  Bassett. 

weeks'  standing  was  obtained.  The  stools  were  muco-purulent  but 
did  not  show  any  blood.  In  only  one  had  blood  been  observed  by  the 
mother  at  the  beginning  of  the  illness.  Among  the  remaining  were 
cases  of  so  called  "dyspeptic  diarrhea." 

After  obtaining  so  many  positive  results  in  cases  of  suspected  infec- 
tion we  undertook  the  study  of  the  stools  of  25  infants  consecutively 
without  reference  to  the  form  of  the  disease  as  inferred  from  the  clini- 
cal symptoms.  We  succeeded  in  recovering  B.  dysenteriae  in  19  cases. 
Of  the  6  cases  3  were  examples" of  simple  marasmus;  one  a  case  of 
chronic  entero-colitis  in  which  blood  had  been  noted  in  the  stool  a 
month  or  more  before ;  and  the  remaining  2  were  of  the  so-called  catar- 
rhal enteritis,  with  fluid  stools  but  without  blood. 

A  Study  of  Stools  of  Normal  Children. — This  undertaking  did  not 
afford  much  hope  of  success  even  if  the  bacilli  were  present  in  small 
numbers.  Our  experience  in  the  examination  of  fecal  stools  even  when 
mixed  with  mucus  had  shown  the  great  difficulty  in  isolating  this  or- 
ganism, when  it  was  greatly  outnumbered  by  the  colon  bacilli.  Until 
some  useful  enriching  method  for  B.  dysenteries  in  mixtures  with  other 
organisms  is  found  negative  results  cannot  be  regarded  as  conclusive. 

We  subjected  to  careful  examination  the  stools  of  25  infants  ranging 
in  age  from  seven  days  to  two  years,  who  had  never  been  ill  with  in- 
testinal disease.  The  dejecta  were  collected  on  sterile  pads  and  plated 
immediately.    The  series  can  be  divided  into  two  classes  : 

Class  I. — Infants  one  week  to  six  months  old.  Stools  yellowish- 
brown,  homogeneous,  fecal ;  no  mucus,  blood  or  pus  present.  Under 
the  microscope  moderate  numbers  of  bacilli  and  cocci  found. 

Class  II. — Older  children.  Stools  large,  semi-solid,  fairly  homo- 
geneous. Color  brownish-green  or  gray.  Odor  offensive.  The  micro- 
scopical examination  did  not  differ  from  that  of  the  first  class. 

The.  same  method  of  bacteriological  study  was  pursued  as  with  the 
sick  children,  but  in  no  instance  was  any  microorganism  obtained  in 
cultures  that  corresponded  to  the  B.  dysenteries.  The  flora,  so  far 
as  studied  by  us,  consisted  of  B.  coli,  B.  lactis  acrogenes,  B.  protens,  and 
Streptococcus  pyogenes. 

An  agglutination  test,  intended  to  be  confirmatory  only,  was  made 
with  the  blood  of  these  children  ( 1 )  with  the  organisms  obtained  from 
their  stools,  and  (2)  with  B.  dy sentence.  Only  negative  results  were 
obtained. 

The  Agghitination  Reaction. — We  look  upon  the  agglutination  reac- 
tion as  of  great  importance  in  the  study  of  this  disease.  After  the 
experience  gained  by  one  of  us   (Duval)  in  the  application  of  the  re- 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


n 


action  to  the  study  of  the  dysentery  of  adults  and  in  view  of  the  results 
of  the  present  investigation  we  are  inclined  to  rank  its  value  along  with 
that  of  the  Gruber-Widal  test  in  typhoid  fever. 

The  technique  of  the  reaction  cannot  be  disregarded.  We  are  con- 
vinced that  by  care  in  its  application  early  cases  and  cases  of  mild  in- 
fection can  be  detected.  When  the  agglutinative  value  of  the  blood  is 
high  no  special  difficulty  presents  itself.  But  when  small  quantities  of 
agglutinin  are  present  in  the  blood  a  proper  ratio  between  the  quantity 
of  serum  and  the  number  of  bacteria  must  not  be  neglected  if  trust- 
worthy results  are  to  be  expected. 

The  suspension  of  bacteria  for  the  test  is  obtained  from  agar-agar 
slants  which  have  been  incubated  for  from  12  to  24  hours.  Older  cul- 
tures and  growths  upon  other  media  are  less  useful.    One  standard  loop 


table  1. 

INFLUENCE    OF     RATIO    BETWEEN    QUANTITY    OF    SERUM    AND    NUMBER    OF    BACTERIA    UPON 

AGGLUTINATION     REACTION. 


Case   from   which 

Case  from  which 

u 

R  e  ac- 

Organism. 

Organism  Was 

Blood  Was 

Dilution. 

0 

t  i  0  n 

Seeding. 

Secured. 

Taken. 

ffi 

Final. 

B.    dysent. 

Harris 

Bedford 

1-20 



_ 

Heavy. 

B.    dysent. 

Harris 

Bedford 

1-20 

+ 

+ 

Light. 

B.    dysent. 

Harris 

Bedford 

1-50 

— 

— 

Light. 

B.    dysent. 

Schuster 

Bedford 

1-20 

— 

— 

Heavy. 

B.    dysent. 

Schuster 

Bedford 

1-20 

+ 

+ 

Light. 

B.    dysent. 

Schuster 

Bedford 

1-50 

~ 

~ 

Light. 

B.    dysent. 

Harris 

McDonnell 

1-20 



Sug. 

Heavy. 

B.    dysent. 

Harris 

McDonnell 

1-20 

+ 

+ 

Light. 

B.    dysent. 

Harris 

McDonnell 

1-50 

— 

— 

Light. 

B.    dysent. 

Schuster 

McDonnell 

1-20 

— 

— 

Heavy. 

B.    dysent. 

Schuster 

McDonnell 

I-2u 

+ 

+ 

Light. 

B.    dysent. 

Schuster 

McDonnell 

I-5O 

— 

Light. 

B.    dysent. 

Harris 

Stabler 

I-20 

_ 



Heavy. 

B.    dysent. 

Harris 

Stabler 

I-20 

+ 

+ 

Light. 

B.    dysent. 

Harris 

Stabler 

1-50 

— 

Light. 

B.    dysent. 

Schuster 

Dukehardt 

I-20 

Sug. 

Heavy. 

B.    dysent. 

Schuster 

Dukehardt 

I-20 

+ 

+ 

Light. 

B.    dysent. 

Schuster 

Dukehardt 

I-50 

— 

— 

Light. 

B.    dysent. 

Harris 

Wolfe 

I-l6 

Sug. 

+ 

Heavy. 

B.    dysent. 

Schuster 

Wolfe 

I-l6 

+ 

+ 

Light. 

B.  typhi,  (con- 

Wolfe 

I-l6 

— 

— 

Light. 

trol) 

+  =  positive;  — ^negative;  Sug.  =suggestive.  "Harris"  is  a  culture  from  the  Philip- 
pines and  was  obtained  from  one  of  the  original  cases  investigated  by  Flexner.  "  Schus- 
ter "  is  Case  III  in  our  series. 


1 8  Charles  IV.  Duval  and  Victor H.  Bassett. 

(oese)  of  surface  growth  should  be  suspended  in  a  tube  (8-10  c.c.)  of 
clear  bouillon.  The  inoculated  bouillon  is  placed  in  the  thermostat  for 
from  15  minutes  to  one  hour,  or  until  a  distinct  but  faint  diffuse  cloud- 
ing of  the  fluid  is  noticeable.  The  blood  is  drawn  into  suitable  tubes 
from  which  the  clear  serum  can  be  separated.  The  dilutions  are  made 
in  the  usual  way  with  graduated  pipettes. 

The  seeding  of  the  bouillon  should  be  controlled.  We  found  the  best 
results  to  come  from  that  seeding  which,  when  bacterial  suspension 
and  diluted  serum  were  mixed,  showed  about  a  dozen  bacilli  to  the 
microscopic  field.  We  wish  to  lay  especial  emphasis  upon  light  seeding 
and  strongly  urge  that  no  bacterial  suspension  be  considered  suitable 
unless  it  fulfils  this  requirement.  The  rule  which  can  be  given  is  some- 
what as  follows  :  serum  in  low  dilutions  may  be  more  heavily  seeded 
than  in  high  ones,  and  powerful  bloods  more  than  weak  ones.  There 
seems  to  be  a  fixed  relation  between  the  amount  of  agglutinating  sub- 
stance and  the  number  of  organisms  with  which  it  will  react.  This 
is  shown  in  Table  Xo.  I. 

The  first  effect  of  positive  sera  is  to  bring  about  a  cessation  of  the 
indeterminate  vibration  (Brownian  movement)  of  the  bacilli.  In  the 
completed  reaction,  in  spite  of  the  light  seeding,  large  clumps  of  bacilli 
result.  In  a  certain  number  of  cases  the  clumps,  instead  of  being  corn- 
met,  show  the  loose  skein  arrangement  described  by  Pfaundler  with 
typhoid  bacilli,  and  noted  with  B.  dysenteries  by  Flexner  and  bv  Kruse. 
The  clumps  may  remain  stationary,  if  evaporation  is  prevented,  for 
from  24  to  72  hours;  or  a  diffuse  growth  through  the  fluid  or  even 
disintegration  of  bacilli  (bacteriolysis)  may  take  place. 

We  do  not  lay  great  stress  upon  the  time  factor  which,  with  our 
present  imperfect  knowledge,  cannot  at  best  afford  more  than  an  em- 
pirical rule.  Bloods  of  high  power  in  low  dilution  begin  to  react  in 
a  few  minutes,  the  reaction  being  complete  in  from  one-half  to  one 
hour.  Still  other  and  quite  powerful  specimens  may  require  from  2  to 
3  hours ;  and  definite  reactions  may  occasionally  be  as  late  as  eight 
hours  in  appearing. 

The  onset  and  duration  of  the  reactions  could  be  studied  in  a  small 
group  of  cases.  Of  13  children  tested  during  the  first  week  of  illness 
ten  gave  positive  and  three  negative  results.  One  case  reacted  on  the 
second  and  one  each  on  the  third,  fourth  and  fifth  days.  Two 
cases  reacted  on  the  sixth,  four  on  the  seventh,  and  one  on  the  eighth 
day.  Of  six  children  tested  in  the  second  week  one  was  positive  on  the 
eighth  day,  one  each  on  the  tenth  and  fourteenth  days ;  the  others  re- 
maining   negative    or    reacting    later.      Of    ten    children    tested    in 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


19 


TABLE   II. 

DURATION       AND      [VARIATION      OF      AGGLUTINATION       REACTION     WITH      BLOOD-SERA     FROM 
CASES    OF    SUMMER    DIARRHEA. 


c 

a 

Results. 

JD 

O   w 

Blood. 

0 
3 

Source  of 
Bacilli. 

Remarks. 

rt   3 

U2 

QQ 

O 

1  hr. 

Final. 

18 

23 

Heiland 

1-16 

Heiland 

Duration  of  acute  stage 

Heiland 

1-16 

Philippine 

— 

— 

of    disease    was    five 

Heiland 

1-16 

B. typhi 

— 

— 

weeks. 

3° 

Heiland 

1-500 

Heiland 

+ 

+ 

Heiland 

1-500 

Philippine 

+ 

+ 

Heiland 

1-16 

B.  typhi 

— 

— 

Heiland 

1-16 

B.  coli 

— 

— 

57 

Heiland 

1-50 

Heiland 

+ 

+ 

Heiland 

1-200 

Heiland 

— 

— 

Case  well   on    sixty-first 

64 

Heiland 

1-16 

Heiland 

— 

— 

day. 

9 

3 

Hoffman 

1-16 

Hoffman 

Duration  four  weeks. 

6 

Hoffman 

1-50 

Hoffman 

+ 

+ 

10 

Hoffman 

1-16 

Hoffman 

— 

— 

Hoffman 

1-16 

Philippine 

— 

— 

8 

10 

Silk 

1-1,000 

Silk 

+ 

+ 

67 

Silk 

1-200 

Silk 

Sug. 

+ 

Silk 

1-200 

Philippine 

Sug. 

-1- 

Silk 

1-300 

Silk 

— 

— 

Silk 

1-16 

Silk 

7 

S 

Friedman 

1-16 

Friedman 

Improved  '  on   19th   day. 

Friedman 

1-16 

Flexner 

— 

— 

Blood    never     reacted 

8 

Friedman 

1-16 

Friedman 

+ 

+ 

in  high  dilution. 

Friedman 

1-16 

Philippine 

+ 

+ 

10 

Friedman 

1-50 

Friedman 

+ 

+ 

Friedman 

1-50 

Philippine 

+ 

4- 

Friedman 

1-16 

B.  typhi 

— 

— 

19 

Friedman 

1-16 

Friedman 

— 

— 

6 

8 

Wolfe 

1-16 

Wolfe 

Duration  of  acute  stage 

17 

Wolfe 

1-40 

Wolfe 

+ 

+ 

was  about  three  weeks. 

Wolfe 

1-16 

B.  typhi 

— 

— 

Relapse  on  50th   day. 

17 

Wolfe 

1-16 

Wolfe 

+ 

+ 

Well  in  10th  week. 

68 

Wolfe 

1-16 

Wolfe 

+ 

+ 

72 

Wolfe 

1-16 

Wolfe 

— 

— 

Out- 

2 

Syracuse 

1-25 

Flexner 

+ 

+ 

This  is  a  blood  sent  to 

pa- 

Syracuse 

1-25 

Silk 

+ 

+ 

us  from  a  case  of  sum- 

tient 

Syracuse 

1-50 

Philippine 

— 

Sug. 

mer  diarrhea  in  Syra- 

Syracuse 

I-IOO 

Philippine 

— 

cuse. 

8 

Syracuse 

1-250 

Philippine 

+ 

+ 

Syracuse 

1-300 

Philippine 

— 

— 

16 

Syracuse 

I-IOO 

Philippine 

+ 

+ 

Syracuse 

1-150 

Philippine 

~ 

"  Philippine  "   is  the  Harris  organism  referred  to  in  Table  I. 


20 


Charles  W.  Duval  and  Victor  H.  B asset t. 


the  third  week,  two  reacted  on  the  fifteenth,  two  on  the  sixteenth,  one 
on  the  seventeenth,  two  on  the  nineteenth,  and  one  on  the  twenty-first 
day.  One  child  giving  a  negative  reaction  on  the  sixteenth  day  gave  a 
positive  one  two  days  later.  Table  No.  II  gives  the  data  as  to  the  varia- 
tion and  duration  of  the  reactions. 

The  agglutination  reaction  is,  therefore,  seen  to  appear  early  and  may 
be  looked  for  with  considerable  confidence  at  the  end  of  the  first  week 
of  illness.  A  small  number  of  the  children  failed  to  react  until  much 
later  and  in  some  cases  there  was  no  reaction. 

Our  present  knowledge  leads  us  to  think  that,  although  the  reaction 
of  agglutination  is  persistent,  it  is  sometimes  lost  or  greatly  reduced 
during  convalescence.  If  death  take  place  late  in  the  disease  the  ag- 
glutinative power  of  the  blood  has  also  suffered  diminution.  On  the 
other  hand,  chronic  cases  have  still  given  good  reaction  as  late  as  the 
third  or  fourth  month  of  the  disease. 


REACTION    OF     "  SILK 


TABLE    III. 

BACILLUS    TO    BLOOD    OF    CASES    OF    SUMMER     DIARRHEA. 


Organism. 

Blood. 

Dilution. 

Result;  One  Hour. 

Silk 

Silk 

1-1,000 

+ 

Silk 

Wiegand 

1-25 

+ 

Silk 

Carr 

1 -400 

+ 

Silk 

Yerzak 

1-50 

+ 

Silk 

Rabin  owitz 

1-1,000 

+ 

Silk 

-   Siegal 

1-20 

+ 

Silk 

Friedman 

1-50 

+ 

Silk 

Tucker 

I-IOO 

+ 

Silk 

Golman 

I-IOO 

+ 

Silk 

Lavine 

1-25 

+ 

Silk 

Love 

1-50 

+ 

Silk 

Proser 

1-20 

+ 

Silk 

Wheeler 

1-20 

+ 

Silk 

Brown 

1-60 

+ 

Silk 

Breitbach 

1-200 

+ 

Silk 

Macomber 

1-200 

+ 

Silk 

Walsh 

I-IOO 

+ 

Silk 

Stevens 

I-IOO 

+ 

Silk 

Plater 

I- 160 

+ 

Silk 

Wolf 

1-40 

+ 

Silk 

Morten  son 

1-25 

+ 

Silk 

Heiland 

1-1,000 

+ 

Silk 

C 

1-1, 000 

+ 

Silk 

Speckerman 

I-IOO 

+ 

Silk 

Bogatsky 

1-16 

+ 

Silk 

Triebasky 

1-50 

+ 

Silk 

Bradley 

I-IOO 

+ 

Silk 

Lucas 

I-IOO 

+ 

Silk 

Bauch 

I-IOO 

+ 

Silk 
Silk 

j-j 

Stabler 

1-25 

+ 

Silk 

Lorber 

1-25 

4- 

Silk 

Dukehardt 

1-25 

"r 

Studies  of  the  Diarrheal  Diseases  of  Infancy. 


21 


The  matter  of  cross-reactions  also  engaged  our  attention.  We  think 
this  important  in  respect  to  the  question  of  identity  of  species  of  the 
organisms  with  which  we  are  working.  Our  opportunities  to  pursue 
this  study  were  good.  In  the  first  place  organisms  from  several  dis- 
tant localities  were  available — Japan,  the  Philippine  Islands,  the  United 
States.  The  last  included  bacilli  obtained  both  from  adult  dysentery 
and   summer  diarrheas.     Besides  many  different  specimens  of  blood 


TABLE   IV. 

AGGLUTINATION    REACTIONS   OF    MT.    WILSON     ISOLATIONS    WITH    ANTI-DYSENTERIC     SERUM. 


Results. 

Isolations. 

Dilution. 

One  Hour. 

Final. 

Schuster 

1-500 

+ 

+ 

Silk 

1-1,000 

Sug. 

+ 

Friedman 

1-200 

+ 

+ 

Riall 

1-400 

+ 

+ 

Hoffman 

I-IOO 

+ 

+ 

Williams 

I-IOO 

+ 

+ 

Wolfe 

l-IOO 

+ 

+ 

Schmelz 

1-500 

+ 

+ 

Mortenson 

1-500 

+ 

+ 

Carr 

1-500 

+ 

+ 

Hickey 

1-500 

+ 

+ 

Rabinowitz 

1-1,000 

+ 

+ 

Heiland 

1-200 

+ 

+ 

Irving 

1-200 

+ 

+ 

Love 

1-200 

+ 

+ 

O'Donnell 

1-200 

+ 

+ 

Soeckerman 

1-500 

+ 

+ 

Walsh 

1-500 

+ 

+ 

Proser 

1-500 

+ 

+ 

Macomber 

1-500 

+ 

+ 

Golman 

1-500 

+ 

+ 

Plater 

1-500 

+ 

+ 

Jackson 

1-500 

+ 

+ 

Stevens 

1-500 

+ 

+ 

Bogatsky 

1-500 

+ 

+ 

Triebasky 

1-500 

+ 

+ 

Lutz 

1-500 

+ 

+ 

Pittle 

1-500 

+ 

+ 

Pursley 

1-500 

+ 

+ 

Tucker 

1-500 

+ 

+ 

Rea 

1-500 

+ 

+ 

Geyhardt 

1-500 

+ 

+ 

Lavins 

1-200 

+ 

'    + 

Lubinsky 

1-200 

+ 

+ 

Marcus 

1-200 

+ 

+ 

Hirste 

1-200 

+ 

+ 

Dukehardt 

1-500 

+ 

+ 

Stabler 

I-IOO 

+ 

+ 

P (outside  case) 

1-200 

+ 

+ 

H (outside  case) 

I-IOO 

+ 

+ 

Hoffman  (301) 

1-400 

+ 

+ 

Stevens  (185) 

1-200 

+ 

+ 

With   dilutions  1-50  or  less,  positive  reactions  were  obtained  in  from  10  to  30  minutes. 


22 


Charles  W.  Duval  and  Victor  H.  Bassett. 


which  could  be  secured  from  children,  anti-dysenteric  serum  obtained 
by  Gay  from  immunized  horses  was  always  available.  For  the 
purpose  of  completeness  a  strain  of  B.  typhosus  was  carried  along  with 
the  other  bacilli,  but  no  further  mention  of  it  need  be  made  as  it  al- 
ways behaved  negatively.     Table  III  gives  the  reactions  obtained  with 


table  v. 

SHOWING    THE    AGGLUTINATION    REACTION    OF     BLOOD    OF  SICK   CHILDREN    WITH    THE    DYS 
ENTERIAE    ISOLATED     FROM    CASES    OF    ACUTE    DYSENTERY. 


Results. 

Suspension  of 

Blood. 

Dilution. 

Bacilli. 

One  Hour. 

Final. 

Shiga  (Japan) 

Lavine 

1-25 

+ 

+ 

Flexner-(  Harris) 

Lavine 

1-50 

+ 

+ 

(Philippine) 

Vedder  and  Duval 

Lavine 

1-50 

+ 

+ 

(New  Haven) 

Kruse    (Germany) 

Lavine 

1-50 

+ 

+ 

Flexner- (Harris) 

Wiegand 

1-40 

+ 

+ 

Flexner-(  Harris) 

Schuster 

1-200 

+ 

+ 

FIexner-(  Harris) 

Pursley 

1-50 

+ 

+ 

Flexner-(  Harris) 

Friedman 

1-25 

+ 

+ 

Flexner-(  Harris) 

Stevens 

1-16 

+ 

+ 

Flexner-(  Harris) 

Silk 

1-1,000 

+ 

+ 

Flexner-(  Harris) 

Wolfe 

1-25 

+ 

+ 

Flexner-(  Harris) 

Carr 

1-50 

+ 

+ 

Flexner-(  Harris) 

Mortensen 

1-16 

+ 

+ 

Flexner-(  Harris) 

Yerzak 

1-50 

+ 

+ 

Flexner-(  Harris) 

Hieland 

1-50 

+ 

+ 

Flexner-(  Harris) 

Proser 

1-25 

+ 

+ 

Flexner-(  Harris) 

Wheeler 

1-20 

+ 

+ 

Flexner-(  Harris) 

Love 

1-20 

+ 

+ 

Flexner-(  Harris) 

Brown     (outside  case) 

1-60 

+ 

+ 

Flexner-(  Harris) 

Rea 

1-16 

+ 

+ 

Flexner-(  Harris) 

Walsh 

1-100 

+ 

+ 

Flexner-(  Harris) 

Macomber 

1-50 

+ 

+ 

Flexner-(  Harris) 

Franklin 

1-16 

+ 

+ 

Flexner-(  Harris) 

Tucker 

I- 100 

+ 

+ 

Flexner-(  Harris) 

Golman 

I-IOO 

+ 

+ 

Flexner-(  Harris) 

Siegal 

1-20 

+ 

4- 

Flexner-(  Harris) 

Gordon 

1-16 

+ 

+ 

Flexner-(  Harris) 

Marcus 

1-16 

+ 

+ 

Flexner-(Harris) 

Hirste 

1-16 

+ 

+ 

Flexner-(  Harris) 

Rabinowitz 

1-500 

+ 

+ 

Flexner-(  Harris) 

Irving 

1-200 

+ 

+ 

Flexner-(Harris) 

Breitbach     (outside   case) 

1-200 

+ 

+ 

Flexner-(  Harris) 

C (outside   case) 

1-1,000 

+ 

+ 

Flexner-(  Harris ) 

Burns 

1-50 

+ 

+ 

Flexner-(  Harris) 

H (outside  case) 

1-50 

+ 

+ 

Flexner- (Harris) 

Bedford 

1-20 

+ 

+ 

Flexner-(Harris) 

Stabler 

1-25 

+ 

+ 

Flexner- (Harris) 

Dukehardt 

1-25 

+ 

+ 

Flexner-(  Harris) 

Lorber 

1-25 

+ 

+ 

Flexner-(  Harris) 

Bogatsky 

1-25 

+ 

+ 

Flexner-(  Harris) 

Boehm 

1-16 

+ 

+ 

Flexner-(  Harris) 

Syracuse     (outside   case) 

1-250 

+ 

+ 

Note: — B.  typhosus  used  as  control  was  negative  in  1-16  dilutions. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  23 

the  bacillus  from  "Silk"  child  (Case  VIII)  towards  a  number  of  blood 
sera  from  cases  of  summer  diarrhea.  Table  IV  gives  the  reactions  with 
anti-dysenteric  serum  and  the  bacilli  isolated  from  the  Mount  Wilson 
cases  of  summer  diarrhea.  Table  V  shows  the  cross-reactions  between 
the  blood  of  the  sick  children  and  the  bacilli  obtained  from  cases  of 
acute  dysentery  chiefly  in  adults.  The  interactions  of  sera  and  bacilli 
from  many  sources  is  clearly  shown. 

We  also  studied  the  agglutination  of  B.  coli,  isolated  from  stools, 
with  the  sera  of  children  ill  with  diarrhea.  Our  results  can  be  stated 
briefly.  In  a  fair  number  of  cases  the  sera  reacted  positively  with  the 
particular  variety  of  colon  bacillus  isolated  from  a  given  case  but  usu- 
ally only  in  dilutions  of  1:16.  In  two  instances  only  out  of  50  cases 
were  reactions  obtained  in  1  125  dilutions.  Cross  reactions  were  never 
secured. 

Is  the  bacillus  of  dysentery  motile  in  artificial  cultivation?  The 
difference  of  view  expressed  by  Shiga  and  Flexner  on  the  one  hand, 
and  Kruse  and  Martini  and  Lentz1  upon  the  other,  makes  it  desirable  to 
add  another  word  upon  the  question  under  dispute,  especially  as  we 
have  been  successful  in  devising  a  method  through  which  it  is  possible 
to  develop  motility  in  the  several  varieties  of  bacilli  now  known.  Shiga 
from  the  beginning  of  his  studies  claimed  motility  for  his  bacillus,  and 
Flexner  described  locomotion  in  the  bacilli  isolated  by  him  in  the  Philip- 
pines although  it  was  not  afterwards  detected  by  him  in  his  artificial 
cultivations.  Vedder  and  Duval  failed  to  discover  motility  in  the  ba- 
cilli obtained  by  them  from  cases  of  acute  dysentery  studied  in  this 
country,  while,  through  a  modification  of  Van  Ermengenrs  method, 
they  succeeded  in  staining  long,  wavy,  peritrichous  flagella  about  the 
bacilli  upon  specimens  of  Shiga's,  Flexner's,  and  Kruse's  organisms. 
The  proof  of  the  existence  of  flagella  indicated  the  occurrence  of  mo- 
tility under  suitable  circumstances,  and  the  determination  of  favorable 
conditions  has  now  been  accomplished. 

The  method  of  developing  motility  is  applicable  to  cultures  recently 
isolated  or  those  cultivated  indefinitely  outside  the  body.  In  the  former 
case  a  guinea-pig  is  inoculated  intraperitoneally  with  a  dose  of  the 
culture  that  will  cause  death  in  24-36  hours.  From  the  peritoneal  exu- 
date a  transplantation  is  made  into  acid  bouillon2  which  is  incubated 

xThe  publication  of  Martini  and  Lentz  (Zeitschr.  f.  Hygiene  u.  Infectionskr., 
1902,  XLI,  540)  appeared  later  than  this  work,  but  as  they  are  so  dogmatic  in 
their  statement,  especial  reference  is  made  to  their  negative  statement. 

2Acid  bouillon  prepared  from  finely  cut,  lean  beef,  in  the  proportion  of  500 
grms.  to  the  litre  of  distilled  water.     After  standing  24  hours  in  the  ice-box,  the 


24  Charles  W.  Duval  and  Victor  H.  Bassett. 

over  night.  The  bacilli  are  non-motile.  If  now  transplantations  are 
made  successively,  from  time  to  time,  into  test  tubes  of  the  acid  bouil- 
lon, as  quickly  as  the  tubes  become  cloudy  from  growth,  motion  will 
be  discovered  within  from  24  to  36  hours.  The  successive  transplanta- 
tions may  be  required  every  one-half  to  one  hour  during  fourteen  to 
sixteen  hours,  a  long  working  day,  in  order  to  bring  about  visible 
motion  in  the  organism. 

In  some  instances  even  better  results  were  obtained  by  diluting  the 
acid  bouillon  with  sterile  distilled  water  in  the  proportion  of  5-10  drops 
of  the  former  to  10  c.c.  of  the  latter. 

This  method  is  somewhat  laborious,  but  it  is  the  only  one  with  which 
we  have  succeeded  invariably.  When  applied  to  older  stock  cultures  it 
must  be  further  elaborated.  The  agar-agar  cultures  used  for  inocula- 
tion must  be  given  in  such  quantity  as  to  cause  the  death  of  a  guinea- 
pig  in  from  24  to  48  hours.  From  the  peritoneal  exudate  a  tube  of  acid 
bouillon  is  inoculated;  from  this  culture,  incubated  for  24  hours,  a 
second  animal  is  inoculated  and  from  the  acid  bouillon  culture  obtained 
from  this  guinea-pig  a  third  one  is  inoculated.  From  this  third  tube,  in- 
cubated for  24  hours,  successive  subcultures  are  prepared  and  examined 
at  frequent  intervals  as  already  stated.1 

The  motion  of  the  bacilli  is  unmistakable,  although  not  all  in  a  given 
field  are  motile.  The  motion  is  a  tumbling  one  which  carries  the  mov- 
ing bacilli  into  the  depth  of  the  fluid  and  up  and  down  across  the  field 
of  the  microscope.  It  is  easily  distinguished  from  even  the  most  active 
Brownian  movements. 

Significance  of  the  Results.  The  studies  presented  in  this  paper 
leave  little  doubt  of  the  causal  relation  of  B.  dysenteries  to  the  summer 
intestinal  diseases  of  children  in  the  cases  studied.  The  proof  of  this 
relationship  which  we  have  brought  forward  in  this  paper,  is  equiv- 
alent to  that  regarded  as  sufficient  to  prove  an  association  of  cause  and 
effect  between  the  same  bacillus  and  adult  dysentery.  The  conclusion 
that  the  bacillus  of  dysentery  is  an  important,  if  not  the  most  important, 
cause  of  the  summer  diarrheas  of  children  seems,  therefore,  justifiable. 
In  how  far  the  presence  of  the  bacillus  may  account  for  the  general 
diarrheal  diseases  among  children,  both  in  the  summer  and  winter,  a 

fluid  is  expressed,  3  grm.  sodium  chloride  and  10  grm.  peptone  are  added,  and 
the  whole  is  boiled,  filtered,  and  tubed.  The  reaction  should  be  decidedly  acid, 
and  the  bacillus  of  dysentery  should  grow  abundantly  in  24  hours  producing  a 
heavily  clouded  suspension. 

'Our  thanks  are  due  to  Professor  Welch  for  drawing  our  attention  to  the  use 
of  acid  bouillon  for  demonstrating  motility. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  25 

larger  study,  embracing  a  wide  range  of  cases  of  intestinal  disturb- 
ances and  distributed  over  a  wide  area,  alone  can  determine. 

The  differences  between  the  pathological  changes  seen  in  adult  ba- 
cillary  dysentery  and  those  in  the  summer  diarrhea  of  infants,  as  well 
as  the  variations  met  with  in  the  latter  disease  itself,  might  well  lead 
one  to  question  the  fact  that  one  organism  is  capable  of  producing  such 
diverse  lesions.  But  our  present  knowledge  of  the  varying  effects  of 
pathogenic  organisms  upon  the  animal  body  is  such  as  to  weaken  argu- 
ments based  upon  such  theoretical  objections. 

As  yet,  it  would  be  premature  to  conclude  from  our  studies  that  all 
cases  of  summer  diarrhea  are  caused  by  the  B.  dysenteriae.  There  are 
needed  studies  of  additional  cases  of  summer  diarrhea  and  also  winter 
diarrhea  of  children  with  the  view  of  discovering  the  presence  of  the 
dvsenterv  bacillus  and  also  the  occurrence  of  the  agglutination  reaction. 


CLINICAL  SUMMARY  OF  CASES  OF  SUMMER  DIARRHEA 

STUDIED  AT  THE  THOMAS  WILSON  SANITARIUM, 
BALTIMORE,   DURING   SUMMER   OF    1902. 

BY  J.   H.   MASON  KNOX,   JR.,  PH.D...   M.D., 
Physician   in   charge,   Assistant   in   Pediatrics,   Johns   Hopkins   University. 

The  results  of  the  bacteriological  study  carried  out  by  Messrs.  Duval 
and  Bassett,  as  given  in  the  preceding  paper,  make  a  brief  description 
of  the  clinical  course  of  the  cases  highly  desirable.  Ten  cases  are 
included  in  the  summary  in  which,  although  the  specific  organism  was 
not  isolated,  the  blood  of  the  patients  in  high  dilution  agglutinated  the 
dysentery  bacilli. 

The  ages  of  the  patients  ranged  from  three  weeks  to  four  years : 

From  3  weeks  to  6  months 15  cases 

6  months  to  12  months 22       " 

"     12  months  to  18  months 9 

"     18  months  to  24  months 5 

Above  24  months 1  case 


52  cases 

Of  the  52  cases,  thirty-six  occurred  in  children  under  one  year,  and 
forty-five  of  the  patients  were  not  older  than  eighteen  months.  Of 
the  whole  number  the  only  case  recorded  over  two  years  old  was  that 
of  a  child  four  years  of  age  who  presented  symptoms  more  like  those 
of  adult  dysentery. 

An  effort  was  made  in  each  instance  to  learn  the  character  of  the 
food  and  water  taken  before  the  onset  of  the  illness. 

The  raw  milk  used  was  usually  bought  from  small  grocery  stores 
near  by.  Of  the  33  cases  in  which  positive  information  as  to  water 
could  be  obtained,  it  was  found  in  30  that  the  water  supplied  to  the 
baby  was  unboiled.  Sometimes  this  unboiled  water  was  used  as  a 
diluent  of  the  food,  but  often  it  was  given  between  feedings.  (In 
but  3  infants  it  is  stated  that  only  boiled  water  was  used  both  with 
and  between  the  feedings. )  In  the  7  cases  in  which  the  attacks  oc- 
curred in  breast  fed  babies,  all  received  unboiled  water  between  their 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


27 


feedings.  Of  the  8  infants  fed  on  boiled  or  sterilized  milk,  only  two 
were  given  boiled  water  exclusively.  Other  errors  are  perhaps  note- 
worthy, as  in  the  case  of  children  of  one  year  old  or  younger  who  were 
fed  regularly  at  the  family  table. 

It  is  difficult  to  speak  from  personal  experience  about  the  manner 
of  onset,  because  some  days  elapsed  between  the  beginning  of  the 
symptoms  and  the  admission  to  the  sanitarium.  In  the  majority  of 
cases  seen  in  the  first  week  of  illness,  the  attack  in  which  the  child  was 
admitted  was  usually  its  first  sickness,  the  history  being  that  the  pa- 
tient, after  a  day  or  two  of  languor,  was  suddenly  seized  with  diarrhea, 
succeeded  or  accompanied  by  vomiting  and  sometimes  by  abdominal 
pain.  Generally  there  was  a  rise  in  temperature  with  considerable 
constitutional  disturbance.  Although  most  of  the  patients  admitted 
had  already  passed  this  stage,  the  history  of  an  acute  onset  was  usually 


Cases. 

Water. 

Boiled. 

Unboiled. 

Not  Stated. 

7 

11 

16 

1 

13 

7 

Breast  fed  plus  condensed  milk.. 
Cow's  milk  boiled  or  Pasteurized. .. . 

2 

6 

13 

1 

3 

3 
3 

Raw  cow's  milk  plus  condensed  milk 

1 

9 

Total  

50 

3 

30 

17 

definite.  After  the  acute  symptoms  subsided,  the  patient  under  favor- 
able conditions  and  proper  treatment,  went  on  to  convalescence  in  from 
a  few  days  to  three  weeks ;  but  if  the  infection  was  more  virulent  or 
the  resistance  of  the  patient  low,  there  was  progressive  loss  of  weight, 
continued  fever,  and  evidence  of  inflammatory  products  in  the  dejecta. 
Of  the  severer  grades  of  infection  there  were  many  examples  in  our 
series.  The  temperature  range  was  as  a  rule  not  very  high,  varying 
usually  between  97  °  and  102 °  F.  It  was  usually  irregular  and  higher 
the  more  acute  the  illness.  Fatal  cases  often  showed  a  considerable  rise 
ante-mortem. 

Vomiting  accompanied  the  diarrhea  at  the  onset  in  15  cases  in  our 
series.  During  the  course  of  the  illness  no  history  of  vomiting  was 
obtained  in  13  cases,  while  in  29  it  was  described  as  moderate,  and  in 
10  as  excessive. 


28  J.  H.  Mason  Knox,  Jr. 

A  brief  description  of  the  stools  is  entirely  inadequate  to  picture  the 
variety  in  appearance  and  consistency  exhibited  by  the  dejecta.  Nearly 
all  of  the  stools  were  semi-fluid  and  consisted  in  part  at  least  of  mucus. 
They  varied  in  number  from  I  to  30  in  twenty-four  hours  and  were 
of  all  possible  shades  of  color  from  yellow  to  grass  green ;  some  con- 
sisted mostly  of  fecal  matter  while  others  were  entirely  without  it. 

The  presence  of  blood  in  the  stools  was  carefully  noted.  In  a  series 
of  forty-eight  cases  this  symptom  was  especially  observed  : 

No  blood  throughout  the  course  of  the  disease  in 13  cases 

Occasional  fleck  or  tinge  of  blood 18       " 

Blood  moderate  in  amount,  but  inconstant 10      " 

Blood  considerable  and  fairly  constant 6      " 

Stool  composed  largely  of  blood 1  case 

Total 48  cases 


When  blood  makes  its  first  appearance  late  in  the  disease  and  is  as- 
sociated with  pus,  it  indicates  the  existence  of  an  inflammatory  process 
and  is  of  unfavorable  significance.  In  many  of  the  cases  in  which  a 
considerable  amount  of  blood  was  present,  pus  was  also  apparent  to 
the  naked  eye  and  leucocytes  were  found  on  microscopical  examination. 

The  length  of  time  the  patients  remained  in  the  sanitarium  averaged 
about  two  weeks. 

Treatment. — Usually  an  initial  purge  of  castor  oil  or  calomel  was 
administered.  Milk  was  always  stopped  entirely  in  the  acute  stage 
and  resumed  gradually  only  as  the  symptoms  subsided.  In  its  stead 
thin  cereal  gruels  with  or  without  egg  albumen  were  substituted,  often 
mixed  with  broth.  Whey  was  used  in  many  instances  and  found  to 
be  well  borne  and  a  convenient  step  in  the  return  to  a  milk  diet.  Gas- 
tric lavage  was  employed  for  excessive  vomiting.  The  colon  was  irri- 
gated in  selected  cases  once  or  twice  a  day,  either  with  salt  solution  or 
a  mild  astringent  solution.  Where  there  had  been  great  loss  of  fluid 
because  of  the  frequency  of  the  stools,  and  symptoms  of  toxemia  were 
present,  hypodermic  saline  infusions  were  employed.  In  general  drugs 
were  used  sparingly  and  only  for  particular  symptoms.  The  following 
table  shows  the  result  in  49  cases  : 

Discharged  cured 20 

improved    14 

unimproved    6 


Died 


9 


49 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  29 

.because  of  the  great  difficulty  in  obtaining  a  reliable  clinical  basis 
of  classification,  any  attempt  at  a  grouping  of  the  summer  diarrheas 
must  be  regarded  as  tentative.  From  a  study  of  the  histories  of  these 
fifty-two  cases  of  infection  with  the  same  microorganism,  we  may  divide 
them  into  two  groups. 

I.  Acute  Gastro-intestinal  Infections  (dyspeptic  diarrhea)  of  which 
there  were  18  exampies.  This  group  showed  little  or  no  evidence  of 
being  associated  with  destructive  intestinal  lesions. 

II.  Ileo-colitis  (dysentery  or  inflammatory  diarrhea)  of  which  there 
were  34  examples.  In  this  group  often  the  early  stages  of  the  disease 
were  similar  to  Group  I ;  but  the  greater  prostration,  the  longer  dura- 
tion, the  character  of  the  stools,  and  at  times  the  fatal  termination  in- 
dicated the  presence  of  inflammatory  processes  in  the  intestines. 

It  is  well  known  that  the  victims  of  summer  diarrhea  are  chiefly  the 
weak  and  badly  nourished  children  of  the  poor,  who  possess  but  little 
resistance.  The  disease  may  be  a  terminal  infection,  often  a  mild  one, 
which  ends  a  protracted  period  of  malnutrition.  This  was  the  history  of 
11  of  our  cases  in  which  the  intestinal  disease  succeeded  a  long  period 
of  wasting.  Of  these  11  cases,  4  properly  belong  to  Group  I.  and  7 
to  Group  II.  In  two  cases  acute  nephritis  complicated  the  intestinal  in- 
fection and  was  the  direct  cause  of  death.  In  one  case  the  diarrhea 
was  concurrent  with  an  attack  of  lobar  pneumonia. 

But  little  can  be  said  of  the  pathological  changes  from  personal  ex- 
perience, as  only  three  of  the  fatal  cases  came  to  autopsy.  One  be- 
longed to  Group  I.  and  two  to  Group  II.  The  following  is  a  brief 
summary  of  the  findings  in  these  cases ;  the  state  of  the  gastro-intesti- 
nal tract  only  being  given  in  detail : 

Case  I. — Stomach :  mucosa  pale  and  smooth.  Small  intestine :  no  disten- 
sion;  mucosa  pale,  Peyer's  patches  moderately  swollen;  no  especial  injection 
of  the  vessels  and  no  ulceration.  Large  intestine :  the  general  condition  of  the 
mucosa  resembled  that  of  the  small  intestine,  but  one  or  two  of  the  enlarged 
lymphatic  nodules  showed  a  minute  superficial  loss  of  substance.  The  mesen- 
teric glands  were  enlarged,  the  swelling  being  noticeable  chiefly  in  the  glands 
of  the  lower  colon  and  rectum. 

This  case  was  complicated  with  nephritis.  The  urine  during  life  contained 
albumin,  pus  cells  and  numerous  casts.  The  kidneys  were  large,  pale,  and  cloudy. 
Patches   of  consolidation  existed  in  the  dependent  parts  of  the  lungs. 

Case  II. — The  stomach  and  duodenum  appeared  to  be  normal.  The  ileum 
showed  throughout  its  length  small  hemorrhages,  but  no  ulceration  was  detected. 
The  jejunum  in  its  upper  third  presented  a  similar  appearance  to  that  of  the 
ileum,  but  the  pathological  process  lessened  and  disappeared  higher  up  in  the 
intestine.  The  patches  of  Peyer  were  swollen  but  not  ulcerated.  The  entire  colon 
was  dilated ;    its  mucous  membrane  was  thickened  and  the  surface  covered  with 


30  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

bloody  mucus.  In  the  mucosa  were  scattered  hemorrhages  and  losses  of  sub- 
stance, varying  from  a  pin's  head  to  a  split  pea  in  size,  the  edges  being  irregular 
and  infiltrated  with  blood.  The  meso-colic  glands  were  markedly  swollen  and 
the  general  mesenteric  glands  were  congested  and  somewhat  enlarged.  The  left 
lung  showed  scattered  areas  of  consolidation. 

Case  III. — The  small  intestine  was  thin  and  pale  and  showed  no  focal  changes 
except  a  few  small  areas  of  congestion  in  the  lower  ileum.  The  mucosa  of  the 
descending  colon  was  thickened  and  hyperemic,  its  surface  irregularly  pitted  but 
not  showing  definite  ulceration.  On  the  other  hand,  the  mucosa  of  the  transverse 
colon,  cecum  and  ascending  colon  showed  groups  of  small  ulcers  apparently  af- 
fecting the  solitary  nodules.  All  the  mesenteric  glands  were  swollen  and  red- 
dened.    The  base  of  the  left  lung  contained  a  consolidated  area. 

The  pathological  conditions  above  noted  while  differing  somewhat 
among  themselves,  differ  essentially  from  the  lesions  found  in  adults, 
and  even  in  children,  in  the  acute  dysenteries  from  which  hitherto  B. 
dysenteriae  (Shiga)  has  been  obtained.  Although  the  lesions  in  the 
intestine  in  the  three  cases  given  present  differences,  they  are  not  such 
as  to  entirely  preclude  their  reconciliation  with  one  pathological  proc- 
ess of  which  they  are  merely  expressions  of  degree,  duration,  etc.  In 
view  of  the  fact  that  in  all  the  B.  dysenteriae  was  found,  the  question 
arises  whether  the  essential  identity  of  the  lesions  may  not  well  be 
considered,  and  a  revision  of  the  nomenclature  of  summer  diarrhea 
be  attempted  upon  an  etiological  basis,  the  beginning  of  which  through 
the  work  of  Duval  and  Bassett  we  have  now  secured. 

There  are  many  questions  bearing  upon  the  pathology  of  the  infantile 
intestinal  diseases  that  with  the  advance  made  may  now  be  regarded  as 
open  to  solution.  Among  the  most  important  is  the  habitat  in  nature 
of  the  Shiga  bacillus,  the  modes  of  its  entrance  into  the  body,  the  pos- 
sible role  played  by  insects,  especially  by  flies,  in  its  dissemination  and 
the  influence  of  predisposing  factors,  such  as  poor  and  improper  food, 
the  manifold  improprieties  in  the  care  of  infants,  the  effects  of  high 
temperatures,  as  in  the  warm  summer  months,  and  other  possible  con- 
tributory causes  to  infection  which  may  well  be  as  important  as  the 
mere  presence  of  the  infecting  organism  itself. 


INVESTIGATIONS   DURING  THE   SUMMER   OF    1903. 


INTRODUCTION. 


BY     SIMON     FLEXNER,     M.D. 

At  the  beginning  of  the  summer  of  1903  the  Rockefeller  Institute 
for  Medical  Research  undertook,  under  my  direction,  the  bacteriologi- 
cal investigation  of  children  affected  with  various  forms  of  diarrhea. 
The  investigation  was  carried  out  directly  by  some  12  bacteriologists 
in  the  cities  of  New  York,  Philadelphia,  Boston  and  Baltimore.  The 
conditions  under  which  it  was  conducted  were  briefly  these : 

During  the  previous  summer  the  Rockefeller  Institute  made  a  grant 
of  money  to  Dr.  J.  H.  M.  Knox,  Jr.,  of  the  Wilson  Sanitarium  for 
Children,  for  the  purpose  of  promoting  the  bacteriological  study  of 
infants  suffering  with  so-called  "summer  diarrhea."  This  study  was 
carried  out  by  Messrs.  C.  W.  Duval  and  V.  H.  Bassett  who  discovered, 
in  the  course  of  it,  in  the  dejecta  and  intestines  of  a  high  percentage 
of  the'  children,  a  bacillus  agreeing  in  essential  properties  with  B. 
dysenteriae,  Shiga.  This  bacillus  was  moreover  found  to  undergo  ag- 
glutination with  the  diluted  blood-serum  of  sick  infants  and  to  be 
unacted  upon,  in  this  respect,  by  the  blood  of  healthy  children  or  of 
children  suffering  from  some  other  diseases.  On  the  basis  of  this  find- 
ing of  the  dysentery  bacillus  in  more  than  forty  ill  children,  of  the 
total  failure  to  obtain  it  in  the  stools  of  normal  children,  and  of  the 
serum  reaction,  they  felt  themselves  justified  in  pronouncing  the  micro- 
organism the  probable  cause  of  the  diarrhea  from  which  the  children 
yielding  it  were  suffering. 

A  year  earlier — the  summer  of  1901 — Vedder  and  Duval  investi- 
gated several  outbreaks  of  dysentery  in  adults  in  this  country  and 
found  the  dysentery  bacillus  in  two  institutional  epidemics  and  a  num- 
ber of  sporadic  cases  of  the  disease.  My  previous  studies  upon  tropi- 
cal dysentery,  made  in  1900,  had  led  me  to  experiment  with  the  pro- 
duction of  a  vaccine  of  the  dysentery  bacillus  which  experiments  were 


32  Simon  Flexner. 

later  continued  under  my  direction  by  Dr.  F.  P.  Gay  in  the  Pathological 
Laboratory  of  the  University  of  Pennsylvania.  The  finding  by  Vedder 
and  Duval  of  that  organism  in  this  country  led  Dr.  Gay  and  myself 
to  begin  the  immunization  of  horses  for  the  purpose  of  producing  a 
serum1  which  might  possibly  possess  curative  power  over  the  bac- 
terial dysenteric  diseases  of  the  tropics  and  the  United  States.  The 
discovery  of  Duval  and  Bassett,  which  was  soon  confirmed  by  Woll- 
stein,  gave  at  once  a  far  wider  field  of  usefulness  for  this  hypothetical 
curative  serum. 

The  Rockefeller  Institute  undertook  to  support  an  investigation  of 
the  bacteriology  of  the  "summer  diarrheas"  of  children  and  to  defray 
the  expenses  of  testing,  as  far  as  might  be,  upon  sick  infants  the 
anti-dysenteric  serum  made  from  the  horse  by  the  injection  first  of 
the  dead  cultures  (vaccine)  and  later  of  living  cultures  of  B. 
dysentenae. 

The  plan  of  the  investigation  which  was  adopted  consisted  in  the 
study  of  sick  children  in  several  Eastern  cities — Boston,  New  York, 
Philadelphia  and  Baltimore.  It  was  hoped  in  this  way  to  secure  data 
of  value  in  regard  first,  to  the  question  of  the  local  or  general  occur- 
rence of  the  dysentery  bacillus,  and  next,  to  the  usefulness  of  the 
anti-dysenteric  serum  and  to  its  action  upon  a  considerable  number  of 
the  patients.  I  shall  deal  with  the  question  of  the  bacteriology  of 
the  cases  especially,  leaving  for  others  the  task  of  reporting  the  effects 
of  the  serum  on  children. 

As  the  cause  of  certain,  at  least,  of  the  diarrheas  was  assumed 
to  be  B.  dysenteriae,  a  concrete  problem  was  immediately  presented  for 
investigation.  In  order  that  this  investigation  should  have  the  value 
of  a  consistent  and  moderately  uniform  undertaking  it  was  necessary 
that  the  persons  conducting  the  bacteriological  portion  of  the  work 
should  be  familiar  with  the  study  of  the  bacterial  flora  of  the  de- 
jecta and  the  method  of  isolating  B.  dysenteriae,  as  well  as  the  manner 
of  carrying  out  the  agglutination  tests. 

I  was  fortunate  enough  to  secure  as  aids  upon  whom  the  work  of 
investigation  would  directly  fall  several  bacteriologists  who  had  al- 
ready established  their  ability  in  this  line  of  study.  The  remainder 
of  the  assistants,  while  they  had  not  worked  so  directly  with  the  prob- 
lem before  them,  yet  had  the  advantages  of  a  thorough  training  in  the 
general  subject  of  bacteriology  and  its  methods.  To  provide,  at  the 
outset,  for  uniformity  of  method  of  work  I  arranged  a  brief  course 

'Shiga  had  already  pronounced  favorably   upon  a  curative  serum  from  Japan. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  33 

of  instruction  at  the  Pathological  Laboratory  of  the  University  of 
Pennsylvania  in  which  the  study  of  the  bacillus  of  dysentery  could  be 
pursued.  This  course  was  attended,  in  the  early  part  of  June,  by 
a  number  of  those  who  later  took  part  in  the  investigation,  and  by 
several  physicians  and  advanced  medical  students  who  conducted 
studies  independently  of  the  Institute  in  Washington,  Philadelphia  and 
Albany. 

The  Rockefeller  Institute  secured  the  hearty  cooperation  of 
numerous  hospitals  and  dispensaries  from  which  the  materials  for 
study  were  drawn,  and  of  several  established  bacteriological  labora- 
tories in  which  the  examinations  could  be  conducted.  I  shall  enumerate 
the  chief  sources  of  the  materials  and  places  of  study  : 

Boston :  Floating  Hospital  for  Children ;  Bacteriological  Labora- 
tory of  the  Board  of  Health.  Especial  thanks  and  acknowledgments 
for  many  acts  of  courtesy  are  due  Dr.  Hastings  and  the  visiting  staff 
and  assistants  of  the  Floating  Hospital,  and  Drs.  Durgin  and  Hill  of 
the  Health  Department. 

New  York :  Vanderbilt  Clinic,  Roosevelt  Hospital,  Babies  Hos- 
pital, Foundling  Hospital,  Department  of  Health,  Bellevue  Hospital, 
Post-Graduate  Hospital,  Nursery  and  Child's  Hospital,  Woman's  In- 
firmary and  Sloane  Maternity.  It  will,  I  regret  to  say  be  impossible 
on  account  of  the  lack  of  space  to  thank  adequately  the  large  number 
of  persons  who  promoted  the  investigations  in  New  York.  But  espe- 
cial acknowledgments  are  due  the  New  York  Health  Department 
and  Drs.  Biggs  and  Park  in  particular,  Drs.  La  Fetra  and  Howland 
of  the  Vanderbilt  Clinic,  Dr.  Prudden,  Dr.  Holt,  Dr.  Freeman  and 
the  management  of  the  hospitals  and  dispensaries  that  so  kindly  sup- 
plied materials  or  gave  the  use  of  laboratories  for  this  investigation. 

Philadelphia :  Children's  Hospital,  L  niversity  Hospital,  Patho- 
logical Laboratory  of  the  University  of  Pennsylvania.  Thanks  are 
also  extended  to  the  medical  staff  of  the  hospitals  and  to  Dr.  New- 
mayer  of  the  Jewish  Charity  Dispensary. 

Baltimore :  Wilson  Sanitarium,  Johns  Hopkins  Hospital  and  Patho- 
logical Laboratory  of  the  Johns  Hopkins  Lniversity.  Acknowledg- 
ments for  courtesies  and  privileges  are  due  the  management  of  the 
Wilson  Sanitarium,  and  to  Professor  Welch  and  the  staff  of  the  Chil- 
dren's Dispensary  of  the  Johns  Hopkins  Hospital. 

The  following  is  a  statement  of  the  laboratory  organizations : 

Boston  :  Mr.  A.  I.  Kendall,  assisted  toward  the  end  of  the  season 
by  Mr.  P.  A.  Lewis. 


34  Simon  Flexner. 

New  York  :  College  of  Physicians  and  Surgeons  :  Dr.  C.  W.  Duval 
assisted  by  Mr.  E.  H.  Shorer.  Babies'  Hospital:  Dr.  Martha  Woll- 
stein,  assisted  by  Dr.  Grace  Dewey.  University  and  Bellevue  Hospital 
Medical  College:  Dr.  F.  P.  Gay,  assisted  by  Dr.  E.  McD.  Stanton. 
Woman's  Infirmary  :     Dr.  Louise  Cordes. 

Philadelphia:  University  of  Pennsylvania:  Mr.  P.  A.  Lewis  (until 
transferred  to  Boston). 

Baltimore :  Wilson  Sanitarium :  Dr.  A*.  H.  Bassett,  John  Hopkins 
University:  Mr.  W.  W.  Waite.  associated  for  a  brief  period  with  Mr. 
E.  H.  Shorer. 

The  separate  reports  which  follow,  in  which  the  results  of  each 
laboratory  are  given,  contain  brief  descriptions  of  the  methods  of 
work ;  but  it  will,  perhaps,  be  desirable  to  state  in  this  place  some  of 
the  general  facts  relating  to  the  subject  of  investigation. 

Since  the  demonstration  by  Pfeiffer  of  bacteriolysis  and  the  applica- 
tion of  the  phenomenon  to  the  diagnosis  of  typhoid  fever  by  Widal, 
agglutination  of  bacteria  by  diluted  blood-serum  has  been  much  em- 
ployed in  the  diagnosis  of  bacterial  diseases.  Although  closer  and 
more  searching  study  has  exposed  certain  fallacies  to  which  the  test 
is  subject,  yet  the  latter  ha^e  served  to  establish  more  definitely  the 
limits  of  its  application.  And  hence  the  general  statement,  to  which 
the  exceptions  are  relatively  unimportant,  can  still  be  made,  to  wit : 
agglutination  of  bacteria  by  well-diluted  blood-serum  is  an  indication 
of  infection  with  the  bacteria  agglutinated. 

The  value  of  this  general  fact  becomes  enhanced  if  it  is  shown  that 
under  conditions  of  ordinary  health,  and  in  the  course  of  certain 
forms  of  disease,  this  agglutinative  reaction  is  absent ;  while  at  the 
same  time  it  appears  regularly,  or  at  least  with  great  frequency, 
when  a  definite  kind  of  pathological  state  of  the  body  exists. 

This  form  of  reasoning,  which  led  Shiga  some  five  years  ago  to  a 
renewed  study  of  the  acute  dysentery  of  Japan  with  the  result,  as  is 
now  widely  known,  of  discovering  the  bacillus  which  bears  his  name, 
led  me  a  year  later  (  1900)  to  a  similar  investigation  of  tropical  dysen- 
tery in  Manila  with  a  result  agreeing  in  all  essential  respects  with 
that  of  Shiga.  Since  this  time  and  through  the  use  of  the  same 
methods  the  cause  of  the  dysentery  of  other  countries,  in  temperate 
and  tropical  climates,  has  been  discovered  to  be  identical  with,  or 
closely  allied  to.  Shiga's  bacillus.  The  application  of  the  method  to 
the  study  of  a  group  of  cases  of  infantile  summer  diarrhea  by  Duval 
and  Bassett  gave,  as  has  already  been  stated,  similar  results. 

It  is  unfortunate  for  the  nomenclature  of  bacillarv  dvsenterv  that 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  35 

doubts  and  disagreements  regarding  the  nature  of  certain  strains  of 
dysentery  bacilli  should  have  entered  into  the  discussion  of  the  cause 
of  the  disease.  And  it  is  even  more  unfortunate  that  local  zeal  should 
have  been  permitted  to  usurp  the  place  of  scientific  accuracy  in  es- 
tablishing the  priority  of  discovery  and  the  precise  nature  of  the  ba- 
cillus of  dysentery. 

As  the  type  of  the  bacillus  must  be  taken  the  organism  described 
by  Shiga  in  1898  and  1899.  With  this  type  the  bacillus  isolated  by 
Kruse  in  1901  is  in  such  close  agreement  as  to  be  indistinguishable 
even  by  the  most  refined  tests,  and  hence  for  this  latter  organism 
there  can  be  claimed  no  independent  position.  Kruse's  observation 
has  the  value  of  establishing  the  application  of  Shiga's  discovery  to 
a  class  of  cases  of  dysentery  occurring  in  Germany. 

At  the  time  of  my  investigation  of  tropical  dysentery  I  identified 
the  bacillus  which  I  isolated  as  Shiga's  bacillus.  Since  that  period, 
and  indeed  within  a  short  time,  differences  in  action  of  the  two  bacilli 
upon  certain  fermentable  substances,  and  in  degree  of  agglutination 
with  serum  derived  from  immunized  animals  have  been  described,  so 
that  at  present  the  two  organisms  are  looked  upon  as  representing 
distinct  types  of  dysentery  bacilli.  When  it  is  recalled  that  the  early 
tests  of  agglutination  were  made  with  human  serum,  and  that  the 
action  of  the  bacilli  on  the  sugars  had  been  little  studied,  and,  further. 
that  in  colony- form  and  usual  cultural  properties  no  differences  are 
to  be  seen,  it  becomes  evident  why  the  bacilli  should  have  been  classed 
as  identical. 

Kruse  was  the  first  to  point  out  a  marked  variation  in  degree  of 
agglutination  between  different  strains  of  dysentery  bacilli.  The  two 
sets  of  cultures  which  he  studied  came  respectively  from  an  epidemic 
of  dysentery  occurring  at  Laar  and  several  cases  of  the  disease  which 
arose  in  an  institution  for  the  insane.  On  the  basis  of  the  observed 
difference  he  proceeded  to  designate  the  former  as  the  "true"  and  the 
latter  as  the  "pseudo-"  dysentery  bacilli. 

Even  should  the  fact  of  the  essential  difference  of  the  organisms 
be  admitted  the  appellations  are  most  unfortunately  chosen.  Admit- 
ting for  a  moment,  as  Kruse  would  have  it,  that  the  second  type  of 
bacillus  is  the  cause  of  asylum  dysentery,  it  assuredly  does  not  set 
up  a  condition  that  can  properly  be  termed  "pseudo-dysentery"  ;  and 
if  not  this,  then  the  bacillus  should  not  be  called  "pseudo-dysentery" 
bacillus.  There  has  been  brought  forward  no  evidence  upon  which 
one  of  the  pathological  processes  may  be  assumed  to  be  dysenteric 
rather  than  the  other,  for  the  anatomical  lesions  are  in  essential  agree- 


36  Simon  Flexner. 

ment.  and  mere  chronology  of  investigation  can  hardly  be  taken  as 
distinguishing  the  '"true"  from  the  "false"  organism.  Time  has  con- 
siderably cleared  up  the  distinctions  noted  by  Kruse  and  has  upheld 
his  view  of  the  variation  in  agglutination,  and  it  has  also  shown  us, 
important  physiological  differences  between  the  two  types.  But  while 
this  support  has  been  forthcoming  time  has  shown  his  view  of  the  dis- 
tinct origin  of  epidemic  and  asylum  dysentery  to  be  erroneous.  This 
last  contention  has  been  disproven  especially  by  the  studies  of  Yedder 
and  Duval  of  two  epidemics  of  dysentery  occurring  in  almshouses  and 
insane  asylums  at  Xew  Haven,  Conn.,  and  Lancaster.  Pa.  They  found 
in  certain  of  the  cases  the  "Shiga"  or  "Kruse"  true  dysentery  bacillus, 
and  in  others  the  type  of  bacillus  first  obtained  by  Flexner*  in  the  Philip- 
pines with  which  the  "pseudo-dysentery"  bacillus  of  Kruse  has  been 
found  to  agree. 

Lentz  has  recently  prepared  a  differential  culture  medium  which  has 
seemed  to  distinguish  readily  and  accurately  the  two  types  of  dysen- 
tery bacilli.  By  using  a  medium  containing  mannite  he  found  that 
certain  strains  of  the  bacilli  did  not  act  upon  it  while  others  attacked 
it  with  the  production  of  acid.  Among  the  cultures  tested  by  him 
were  those  of  the  following  origin:  Shiga  (Japan).  Kruse  (Ger- 
many). Duval  (Xew  Haven),  and  Miiller  (Styria),  all  of  which  left 
the  mannite  unaffected,  and  Flexner  (Harris,  Manila),  Strong  (Ma- 
nila ) ,  and  Kruse  ( pseudo-dysentery )  which  attacked  that  substance 
energetically.  These  results  have  been  controlled  by  Martini  (and 
himself)  with  the  serum  of  a  goat  which  had  been  immunized  by 
means  of  a  culture  of  the  first  or  "Shiga"  type  of  the  bacillus  of  dys- 
entery the  agglutination  value  of  which  for  that  type  was  1  :6oo  and 
for  the  second  or  "Flexner-Harris"  type  1  125  to  1  :5c  Hiss  and  Rus- 
sell confirmed  the  studies  of  Lentz  and  introduced  a  valuable  additional 
differential  culture-fluid — their  serum-water  medium. 

The  foregoing  data  upon  the  types  of  dysentery  bacilli  lead  us  to 
conclude  that  the  fact  of  their  general  cultural  agreement  is  over- 
shadowed by  the  differences  displayed  by  them  in  their  action  on 
mannite  and  response  to  a  single  kind  of  artificial  agglutinative  serum. 
And  yet  evidence  is  not  wanting  to  show  that  in  agglutination-value 
the  two  types  are  not  wholly  distinct,  for  which  we  can  adduce  the 
fact  of  the  action  upon  both  types  of  bacilli  of  human  serum  in  cases 
of  dvsenterv  and  "summer"  diarrhea. 


*lhe   special  strain  of  this  bacillus   which  has  been  extensively  studied  came 
from  a  soldier  named  "Harris"';    hence  the  designation  "Flexner-Harris." 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  37 

While  normal  human  serum  in  considerable  concentration  is  with- 
out agglutinative  effect  upon  the  bacilli,  the  serum  of  dysenteries  ag- 
glutinates both  types  of  bacilli  and  often  in  approximately  the  same 
degree.  The  dysentery  bacilli  isolated  in  1902  by  Duval  and  Bassett 
from  children  have  since  been  shown  by  the  studies  of  Gay  and  Duval 
to  consist  exclusively  of  the  "Flexner-Harris"  type ;  and  yet  Duval  and 
Bassett  found  that  the  blood-serum  of  these  children  acted  upon  both 
types  of  bacilli  in  respect  to  agglutination.  Since  the  "Shiga"  type 
of  the  organism  is  supposed  to  agglutinate  less  readily  than  the  "Flex- 
ner-Harris" type  (to  be  less  susceptible  to  chance  agglutinins  according 
to  Kruse  and  Martini  and  Lenz),  the  occurrence  of  active  agglutinins 
in  these  children  for  the  "Shiga"  bacillus  speaks  unmistakably  for  the 
ready  development  in  human  beings,  of  agglutinins  for  both  of  the 
types  of  bacilli  as  a  result  of  infection  with  a  single  type. 

The  serum  of  the  horse  would  seem  to  contain  normally  at  times 
agglutinins  for  a  considerable  number  of  bacterial  species.  Bergez 
has  recently  studied  these  normal  agglutinins  with  especial  reference 
to  certain  water  bacteria.  For  this  purpose  he  employed  anti-dysenteric 
serum  of  the  horse  (supplied  by  me)  and  he  found  that  the  removal 
from  the  serum  of  the  agglutinins  for  those  bacteria  left  the  specific 
agglutinins  for  dysentery  bacilli  practically  intact.  Gay  has  also 
made  cut  that  in  spite  of  the  occurrence  of  natural  agglutinins  in 
horse  serum  for  B.  dysenteriae,  the  artificial  immunizing  with  cul- 
tures of  the  bacillus  increases  the  agglutination-value  of  the  serum  so 
immensely  as  to  render  inconsiderable  and  hence  negligible  for  cross 
testing,  the  normal  agglutinins.  He  ascertained  the  fact  that  as  the  ag- 
glutinins for  one  type  of  the  bacillus  are  raised  by  immunization  that 
the  agglutination-value  of  the  serum  for  the  other  type  rises ;  and  hence 
the  proportion  is  not  a  fixed  one  for  the  two  types  of  the  bacilli,  since 
one  does  not  remain  stationary  while  the  other  rises,  but  that  this 
proportion  is  capable  of  variation  at  will  within  the  limits  of  arti- 
ficial immunization  and  corresponding  agglutinin  production. 
Using  horses'  serum  of  relatively  high  agglutination-value  Gay 
obtained  figures  and  proportions  of  cross  agglutinations  which  showed 
those  of  Martini  and  Lentz,  who  employed  a  weak  artificial  goat's 
serum,  to  be  much  too  low.  Thus  the  serum  of  "Shiga"  horses  gave 
the  proportion  of  6:1  to  30:1  as  regards  the  "Flexner-Harris"  type, 
and  of  "Flexner-Harris"  horses  the  proportion  of  5:1  to  10:1  as  re- 
gards the  "Shiga"  type. 

The  question  of  the  relationship  of  the  types  of  dysentery  bacilli  is 
so  important  that  I  shall  discuss  briefly  another  aspect  of  the  subject. 


3$  Simon  Flexner. 

Dysentery  bacilli  are  subject  to  bacteriolysis  in  vitro  either  by  means 
of  fresh  normal  or  fresh  immune  horses'  serum.  For  the  purpose 
of  studying  the  comparative  bacteriolysis  of  the  two  types  of  bacilli 
both  serums  are  employed. 

Shiga  first  applied  the  method  devised  by  Neisser  and  Wechsberg 
to  the  bacteriolysis  of  dysentery  bacilli,  but  his  study  had  no  reference 
to  the  differentiation  of  the  types.  A  word  upon  the  method  may  be 
in  place  :  A  fixed  quantity  of  normal  fresh  horse's  serum,  incapable 
in  itself  of  producing  bacteriolysis,  will,  in  the  presence  of  a  definite 
amount  of  inactivated  immune-serum,  cause  complete  destruction  of  a 
given  weight  of  dysentery  (or  other)  bacilli.  The  addition  of  more 
or  less  immune-serum  than  is  exactly  required  will  allow  of  greater 
or  less  growth  of  the  organisms,  according  as  a  deficiency  or  an  excess 
of  amboceptors  is  present  in  the  mixture.  An  insufficiency  of  immune- 
serum  prevents  complete  bacteriolysis  by  failing  to  supply  all  the 
amboceptors  needed  to  unite  the  complements  to  the  bacteria ;  an  ex- 
cess of  immune-serum  also  prevents  complete  bacteriolysis  by  introduc- 
ing so  large  a  number  of  amboceptors  as  to  bring  about  their  union 
directlv  with  the  complement  (without  any  attachment  to  the  bodies 
of  the  bacteria )  and  hence  its  deviation  from  the  bacteria.*  Since  it  is 
the  complement  that  destroys  the  bacteria,  should  it  become  deviated 
from  the  bacteria,  then  no  destruction  takes  place. 

Gav,  while  working  under  a  grant  from  the  Rockefeller  Institute, 
in  my  laboratory  at  the  University  of  Pennsylvania,  found  that  the 
bacteriolvsis  of  dysentery  bacilli  as  observed  under  these  conditions, 
was  dependent  upon  the  employment  of  bacilli  and  immune  serum  of 
corresponding  types.  Neither  immune  serums  nor  types  of  bacilli 
were  mutually  interchangeable  in  producing  bacteriolysis,  from  which 
fact  the  conclusion  that  bacteriolytic  variations  serve  to  distinguish  the 
two  types  of  bacilli  could  be  drawn. 

From  the  facts  enumerated  it  will  be  evident  that  the  more  recent 
studies  upon  Bacillus  dysenteriae  have  tended  to  establish  more  and 
more  firmly  the  belief  in  the  existence  of  "types"  of  the  organism. 
Between  these  types  the  similarities  are  perhaps  no  more  important 
than  the  differences  ;  but  no  facts  have  thus  far  been  brought  forward 
which  would  indicate  that  one  rather  than  the  other  acts  pathogenetic- 
ally  upon  human  beings.  This  last  consideration  is  of  commanding  im- 
portance in  respect  to  the  possible  employment  of  an  artificial  immune 
serum  in  combating  infections  with  the  bacilli  in  man. 

*It  is  needless  to  point  out  that  the  explanation  of  the  facts  of  bacteriolysis 
under  the  conditions  named  is  hypothetical. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  39 

Since  the  finer  reactions  tend  to  separate  the  two  types  of  bacilli 
the  question  which  presses  for  solution  is  whether  the  action  of  pro- 
tective immune  serum  is  as  distinct  as  the  mannite,  agglutination  and 
bacteriolytic  reactions.  Upon  the  answer  given  to  this  question  may 
depend  the  practicability  of  using  therapeutically  anti-dysenteric  serum. 

Shiga's  immune  serum  is  polyvalent  and  prepared  by  injecting 
several  strains  of  dysentery  bacilli  into  the  horse.  Whether  or  not  all 
the  strains  employed  represent  the  "Shiga"  type  of  bacillus 
is  not  known ;  for  the  differentiation  now  recognized  was  undiscovered 
when  his  serum  was  first  made.  Indeed,  it  is  not  stated  whether  more 
than  one  type  of  the  bacillus  occurs  in  Japan.  Hence  his  serum  is 
not  adapted  either  to  the  study  of  bacteriolysis  in  the  manner  intro- 
duced by  Gay  or  to  the  testing  of  a  cross  process  of  immunization  such 
as  is  now  to  be  described. 

At  my  request  Dr.  Gay  made  a  careful  and  exact  study  of  cross- 
immunization  of  guinea-pigs  with  the  "Shiga"  and  "Flexner-Harris" 
types  of  bacilli  and  immune  serums.  Fortunately  an  unlimited  quantity 
of  serum  was  available  as  we  had  had  several  horses  in  process  of 
immunization  with  the  different  types  during  a  period  of  two  years.* 

As  the  dysentery  bacillus  tends  to  diminish  in  virulence  when  culti- 
vated outside  the  body  it  is  necessary  that  a  standard  of  activity  be 
established  and  maintained  by  frequent  passage  of  cultures  through 
guinea-pigs.  By  choosing  animals  of  a  fixed  weight  and  the  injec- 
tion of  a  determined  quantity  of  active  culture,  death  takes  place  regu- 
larly in  from  18  to  24  hours.  The  suspensions  of  the  bacilli  were 
injected  intraperitoneally,  and  when  immune  serum  was  employed  it 
was  introduced  beneath  the  skin. 

The  experiments  on  cross-immunization  and  infection  proved  to  be 
very  important  in  that  they  showed  that  the  protective  power  of  the 
serum  is  a  factor  which  fails  to  proceed  hand  in  hand  with  bacterioly- 

*It  is  proper  in  this  place  to  acknowledge  our  indebtedness  to  the  Rockefeller 
Institute  for  Medical  Research  which  promoted  by  money  grants  the  study  of 
immunization,  and  to  the  H.  K.  Mulford  Company  of  Philadelphia  which  gener- 
ously provided  the  large  number  of  horses  used  in  the  course  of  this  study  and 
the  subsequent  tests  of  the  immune  serum  upon  children.  The  H.  K.  Mulford 
Company  also  rendered  us  invaluable  aid  through  their  laboratory  staff,  and  we 
wish  to  thank  the  gentlemen  composing  it,  and  especially  Drs.  Kinyoun  and 
Lincoln,  for  their  many  courtesies  and  the  ready  and  very  able  help  which  they 
rendered  us.  It  was  a  great  convenience  later  on,  while  conducting  the  tests  upon 
children  suffering  from  diarrhea,  to  have  the  immune  serum  provided  us  in 
sterile  glass  syringes  for  immediate  use,  which  the  H.  K.  Mulford  Company  sup- 
plied without  cost. 


40  Simon  Flexner. 

sis  by  serum,  and  that  the  latter  phenomenon  is  not  a  measure  of  the 
possible  usefulness  of  the  serum  as  a  therapeutic  agent.  On  the  other 
hand,  the  experiments  also  proved  that  the  protective  power  of  the 
serum  is  greater  for  an  organism  of  a  corresponding  than  for  a  so- 
called  "crossed"  type.  Stated  in  actual  figures  almost  twice  the  quan- 
tity of  serum  is  needed  to  give  for  the  "crossed"  a  protection  equal  to 
that  given  for  the  same  type  of  bacillus. 

At  the  beginning  of  the  summer  of  1903  Bacillus  dysenteriae,  first 
found  by  Shiga  in  Japan  in  1898-99,  had  been  proven  to  be  intimately 
associated,  and  probably  the  cause  of  acute  endemic,  epidemic,  sporadic 
and  institutional  dysentery  over  practically  all  the  world.  The  or- 
ganism had  further,  through  the  studies  of  Duval  and  Bassett,  been 
shown  to  bear  a  similar  intimate  relationship  with  a  certain  class  of 
cases  of  diarrhea  arising  in  children  during  the  warm  summer  months 
and  by  Wollstein  to  such  cases  occurring  in  the  winter.  A  closer  study 
of  the  bacillus,  had  led  to  its  separation  into  two  groups  according  to 
certain  distinctive  reactions.  Shiga  had  already  produced  a  polyvalent 
immune  serum  with  which  he  had  successfully  treated  the  acute  dysen- 
tery of  Japan,  and  Flexner  and  Gay  had  completed  the  preparation 
of  a  series  of  monovalent  immune  serums  which  they  proposed  to  have 
used  in  the  treatment  of  bacillary  dysentery  in  Manila  and  the  United 
States,  and  of  children  suffering  from  infection  with  the  bacillus  of 
dysentery.  Gay  had  shown  that  an  effective  protection  by  mean  of  im- 
mune serum  is  possible  without  reference  being  paid  to  the  special  type 
of  bacillus  causing  the  infection  or  employed  to  produce  the  anti-dysen- 
teric serum. 

In  the  summer  of  1903,  as  has  been  stated,  I  was  enabled  through  a 
liberal  grant  of  money  from  the  Rockefeller  Institute  for  Medical  Re- 
search and  the  co-operation  of  a  group  of  skilled  bacteriologists  to 
direct  an  investigation  of  the  bacteriology  of  diarrheal  diseases  occur- 
ring in  a  large  number  of  children,  and  to  have  tested  upon  a  number 
of  these  children,  suffering  from  infection  with  Bacillus  dysenteriae,  an 
anti-dysenteric  serum  prepared  from  the  horse. 

The  separate  reports  which  follow  upon  the  bacteriology  of  the 
cases  containing  the  results  arrived  at  by  the  different  workers  have 
been  edited  by  me.  The  results  are,  however,  entirely  the  property  of 
the  workers,  as  my  share  in  the  investigation  consisted  in  the  exercise 
merely  of  a  general  supervision  and  control  which  in  no  vital  way  af- 
fected the  individual  work  of  the  investigation. 

A  separate  and  distinct  report  upon  the  results  of  the  injection  into 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  41 

children  of  the  anti-dysenteric  serum  will  be  included  in  this  publica- 
tion. 

BIBLIOGRAPHY. 

Duval  and  Bassett.     American  Medicine,  1902,  iv,  417. 

Flexner.  Phila.  Medical  Journal,  1900,  vi,  414 ;  Univ.  of  Penna.  Med.  Bulletin, 
1901,  xiv,  190. 

Gay.  Univ.  of  Penna.  Med.  Bulletin,  1902,  xv,  307;  Univ.  of  Penna.  Med. 
Bulletin,   1903,  xvi,  174. 

Gay  and  Duval.     Univ.  of  Penna.  Med.  Bulletin,  1903,  xvi,   177. 

Hiss  and  Russell.     Medical  News,  1903,  lxxxii,  289. 

Kruse.     Deutsche  Med.  Wochenschrift,   1900,  xxvi,  637;    1901,  xxvii,  370. 

Lentz.     Zeitschrift  f.  Hygiene  u.  Infectionskrank.,  1902,  xli,  559. 

Martini  and  Lentz.     Zeitschrift  f.  Hygiene  u.   Infectionskrank.,   1902,  xli,  540. 

Neisser  and  Wechsberg.     Miinchener  med.  Wochenschrift,  1901,  xlviii,  697. 

Park  and  Carey.     Journal  of  Medical  Research. 

Shiga.  Centralbl.  f.  Bakter.  u.  Parasitenkunde,  1898,  xxiii,  599;  1899,  xxiv, 
817,  870,  913 ;    Deutsche  med.  Wochenschrift,  1901,  xxvii,  741,  765,  783. 

Vedder  and  Duval.     Journal  of  Exper.  Medicine,  1902,  vi,  181. 

Warfield.  Bulletin  of  the  Ayer  Laboratory  of  the  Pennsylvania  Hospital,  1903, 
No.  1. 

Wechsberg.     Zeitschrift  f.   Hygiene  u.    Infectionskrank.,    1902,   xxxix,    171. 

Wollstein.     Journal  of  Medical  Research,  1903,   x,  No.  1. 


REPORT  OF  C.  W.  DUVAL,  M.D.,  ASSISTED  BY  E.  II. 
SHORER,   Stud. Med. 

The  study,  the  results  of  which  are  to  be  given  in  this  report,  was 
carried  out  in  the  bacteriological  laboratory  of  the  College  of  Physi- 
cians and  Surgeons,  New  York,  which  was  placed  at  our  disposal 
through  the  kindness  of  Professor  Prudden.  We  cannot  be  too  grate- 
ful to  him  and  to  the  staff  of  the  laboratory  for  the  courtesies  which 
were  shown  us  and  the  thorough  manner  in  which  our  work  was  facil- 
itated. Without  this  cordial  help  and  cooperation  the  results  of  our 
work  must  have  been  less  satisfactory  and  complete  than  we  were  able, 
through  this  assistance,  to  make  them. 

The  entire  number  of  sick  infants,  studied  during  the  months  of 
June,  July,  August  and  September,  was  79.  The  study  actually  began 
on  June  15th,  and  closed  about  the  end  of  September,  continuing, 
therefore,  three  and  a  half  months.  The  materials  of  the  study,  which 
consisted  of  dejecta,  were  chiefly  drawn  from  the  Yanderbilt  clinic. 
Roosevelt  and  Post-Graduate  Hospitals  furnished  six  cases,  and  a  few 
were  private  patients  (see  table).  From  these  cases  we  obtained  the  ba- 
cillus dysenteriae  (Shiga)  in  greater  or  less  numbers  from  75,  or  in 
94  per  cent.,  of  all  the  cases  examined.  The  clinical  symptoms  and 
course  of  the  disease  were  so  varied  as  to  include  all  grades  of  cases, 
from  the  mildest  to  very  severe  forms  of  diarrheal  disease.  And  in 
keeping  with  this  fact  the  stools  which  came  to  us  for  examination 
varied  within  very  wide  limits,  on  the  one  hand  consisting  almost 
wholly  of  feces,  and,  on  the  other,  of  blood  and  mucus  practically  with- 
out fecal  contamination. 

Isolation  of  Bacillus  Dysenteriae. — The  character  of  the  dejecta 
with  which  we  worked,  as  compared  with  that  studied  by  Duval 
and  Bassett,  led  us  to  modify  the  technique  recommended  bv  the 
latter  in  their  publication.  Since  Duval  and  Bassett  dealt  especiallv 
with  stools  containing  mucus  and  blood  and  had  their  chief  success 
with  that  type  of  stool,  and  as  the  material  furnished  us  con- 
tained many  specimens  from  which  mucus  and  blood  in  more  than 
notable  quantities  were  absent,  we  found  that  a  more  rigid  examination 
than  previously  made  would  be  required  either  to  exclude  with  toler- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  43 

able  certainty  the  finding  of  the  bacillus,  or  to  demonstrate  it  among 
the  large  number  of  bacteria  with  which  it  was  often  associated  in 
cultures. 

We  found  the  use  of  fresh-stool  specimens  of  the  utmost  im- 
portance, i.e.,  specimens  obtained  immediately  after  passage.  While 
stools  rich  in  the  bacilli  may  be  dealt  with  successfully  after  a  longer 
interval  of  time,  or  may  be  made  to  yield  the  dysentery  organism  with 
less  trouble  than  the  process  we  are  to  describe  involves,  success  with 
many  specimens  can,  we  think,  be  obtained  only  by  the  exercise  of 
laborious  care.     The  procedure  which  we  pursued  is  as  follows : 

Mucus  is  to  be  selected  for  the  plating,  and  when  this  is  attached 
or  adjacent  to  fecal  matter  it  is  to  be  teased  away  from  the  latter  by 
means  of  a  stiff,  sterile  platinum  loop.  The  mucus  is  now  suspended 
in  normal  saline  solution  or  bouillon,  the  mixture  well  shaken  and  set 
aside  for  a  few  minutes  in  order  to  permit  the  washed  mucous  flakes  to 
settle.  The  upper  two-thirds  of  the  fluid  becomes  clear  of  visible  par- 
ticles, but  presents  a  cloudy  appearance,  due  chiefly  to  the  suspended 
bacteria.  From  this  cloudy  fluid  are  prepared  twelve  (12)  Petri  plates 
in  neutral  agar-agar,  using  one  to  two  loopfuls  of  the  suspension  for 
each  plate.  The  decision  whether  to  employ  one  or  two  loops  for  the 
plating  will  depend  upon  the  degree  of  cloudiness  which  is  brought 
about  by  the  number  of  suspended  bacteria. 

By  proceeding  in  this  way  and  plating  from  two  separate  suspen- 
sions of  mucus  we  obtained  about  25  plates,  which,  as  a  rule,  is  the 
smallest  number  with  which  we  worked.  The  seeding  of  these  plates 
should  be  regulated  so  that  the  total  number  of  colonies  developing  on 
a  plate  shall  number  between  50  and  too.  By  paying  attention  to  the 
degree  of  cloudiness  of  the  fluid  and  adjusting  to  this  the  number  of 
loops  carried  in  to  the  agar-agar  it  is  easily  accomplished.  We  have 
found  this  method  preferable  to  the  use  of  a  stronger  initial  suspension 
of  bacteria  and  the  employment  of  a  second  and  third  dilution  as  is 
generally  practiced. 

In  incubating  the  plates  are  inverted  and  left  in  the  thermostat  at 
2,7°  C.  from  14  to  18  hours.  At  the  end  of  this  period  every  small 
pearl  gray  colony  is  transplanted  to  Hiss'  semi-solid  medium.  All  col- 
onies are  now  marked  on  the  glass  with  a  wax  pencil  and  the  plates 
kept  inverted  at  room  temperature  for  one  week  at  least,  observations 
upon  the  development  of  new  colonies  being  made  daily.  We  may 
remark  here  that  in  order  to  avoid  the  rapid  desiccation  of  the  agar- 
agar  the  plates  are  not  returned  to  the  thermostat.  As  it  is  of  advantage 
to  have  the  medium  form  a  thin  layer  in  the  plate  so  that  surface  col- 


44  C.   W.  Duval. 

onies  chiefly  develop,  drying  is  to  be  avoided  as  much  as  possible.  All 
new  colonies  which  appear  are  sub-cultured  into  the  semi-solid  me- 
dium. The  character  of  the  growth  of  the  dysentery  bacillus  in  this 
culture  material  will  be  described  presently  but  in  this  place  it  should 
be  stated  that  if  that  bacillus  does  not  appear  among  the  tubes  prepared 
in  this  way,  all  the  markings  are  to  be  erased  from  the  plates  and  every 
small  colony  that  resembles  in  form  and  color  colonies  of  Bacillus  coli 
communis  or  Bacillus  typhosus  is  to  be  transplanted  to  the  semi-solid 
medium. 

The  inoculated  tubes  are  ready  for  examination  after  having  been 
kept  at  3/°  from  3  to  6  hours.  All  tubes  showing  a  cloud  throughout 
are  discarded  for  it  is  brought  about  by  the  presence  of  actively  motile 
bacilli,  among  which  B.  dysenteriae  is  not  contained,  and  all  tubes 
showing  gas  formation  are  also  excluded.  Those  tubes  which  present 
a  slight  haziness  or  show  growth  along  the  needle  track  only  are  tested 
for  gas  production  by  careful  stirring  with  the  platinum  needle.  Any 
disengaged  gas  collects  in  the  form  of  small  bubbles,  and  all  tubes  i:i 
which  these  appear  are  also  put  to  one  side.  Only  such  tubes  as  ex- 
hibit no  bubbles  are  examined  further. 

The  next  step  is  to  test  with  anti-dysenteric  serum  all  cultures  not 
forming  gas  in  which  the  morphology  of  the  organisms  is  that  of 
colon-typhoid  bacilli.  For  this  purpose  a  small  quantity  of  the 
growth  is  suspended  in  salt  solution.  We  used  the  serum  of  the  horse 
supplied  by  Dr.  Flexner  for  carrying  out  these  tests.  All  bacilli  show- 
ing a  positive  agglutination  are  sub-cultured  into  litmus  milk  and  the 
serum-water  medium  of  Hiss.  In  some  instances  we  also  sub-cultured 
into  media  containing  other  sugar,  e.g.,  dextrose,  maltose,  saccharose, 
and  also  dextrin. 

Identification  of  Bacillus  Dysenteriae. — The  usual  plan  which  we 
pursued  in  our  study  was  to  identify  the  bacillus  by  cultural  tests  be- 
fore applying  the  serum  reaction,  for  one  learned  that  the  immune 
serum  of  the  horse  will  sometimes  bring  about  the  agglutination  of  ba- 
cilli which  do  not  agree  culturally  with  the  dysentery  bacillus.  We 
found  some  such  nondescript  bacilli  which  reacted  in  dilutions  of 
1  1500  of  serum. 

The  most  reliance  is  to  be  placed  upon  the  growth  of  the  bacillus  in 
litmus  milk  observed  over  a  period  of  several  weeks.  The  true  organ- 
ism produces  first  acidity,  which  turns  the  fluid  lilac  in  color,  and  after 
some' days  this  initial  acidity  gives  way  and  the  color  returns  to  that 
of  the  control  (amphoteric  reaction  and  first  alkali  production).  The 
next  change  develops  much  more  slowly  and  may  not  become  distinctly 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  45 

visible  for  several  weeks,  when  the  milk  will  show  a  more  marked 
alkaline  reaction  (second  alkali  production),  which  is  the  final  change. 

Although  no  stress  has  been  put  upon  the  consideration  of  the 
colony  form,  growth  upon  agar-agar  slants,  etc.,  these  features  have 
not  been  overlooked ;  but  as  they  are  less  conclusive  than  the  milk-re- 
action, agglutination,  and  the  behavior  of  the  bacillus  in  the  special 
media  mentioned,  their  use  is  not  emphasized  in  this  place. 

In  the  course  of  our  work  we  paid  special  attention  to 
the  types  of  dysentery  bacilli,  which  we  isolated  from  dejecta.  For 
the  differentiation  of  the  two  types — so-called  "acid"  and  "alkaline'' 
types  as  tested  upon  the  litmus-mannite  medium,  we  soon  discarded  the 
use  of  that  material  for  the  mannite-serum-water  medium  of  Hiss.  It 
will  be  found  that  the  latter  is  exactly  as  useful  as  the  former  and  has 
the  advantage  of  being  easily  and  much  more  quickly  prepared — a  gain 
not  to  be  considered  lightly  when  hundreds  of  separate  colonies 
of  the  bacilli  are  to  be  tested.  Whereas  it  requires  48  hours  to  rid 
the  beef  juice  of  all  muscle  sugar  by  means  of  fermentation  (by  the  use 
of  B.  coli  com.)  in  preparing  it  for  conversion  into  a  nutrient  medium, 
the  serum  is  ready  at  once  for  use  without  further  treatment.  If  it  is 
desired  to  have  a  solid  medium,  the  litmus-mannite  agar-agar  can  be 
made  from  peptone  water  without  any  beef  or  even  without  beef  ex- 
tract ;  and  although  the  growth  of  bacilli  may  be  less  vigorous  than  in 
the  samples  containing  beef  it  is  sufficient  for  the  purpose  of  separa- 
ting the  types  of  the  organism. 

In  carrying  out  the  differentiation  of  types  we  carried  into  the 
serum- water  media  (for  we  employed  serum-water  containing  mannite, 
dextrose  and  dextrine  respectively ) ,  every  colony  growing  upon  the 
semi-solid  medium  in  a  characteristic  manner,  and  giving  an  agglutina- 
tion result.  The  interpretation  of  the  action  of  the  bacilli  upon  these 
media  is  important  and  offers  no  special  difficulty.  Since  acid  produc- 
tion is  associated  with  coagulation  of  the  medium,  and  both  types  of 
bacilli  attack  dextrose  with  the  formation  of  acid  it  follows  that  all 
dysentery  bacilli  bring  about  coagulation  of  the  serum-water  dextrose 
medium.  Since,  on  the  other  hand,  the  "Flexner-Harris''  type  of  organ- 
ism splits  mannite  and  the  "shiga"  type  does  not,  the  former  also  brings 
about  coagulation  of  the  serum-water  mannite  fluid.  The  use  of  a 
special  fluid  in  which  dextrin  supplants  the  sugars  serves  to  separate 
still  further  the  "Flexner-Harris"  type  of  organism  into  two  groups — - 
fermenter  and  non-fermenter  of  dextrine,  or,  according  to  Hiss  and 
Russell — B.  dysenteriae  "Harris,"  from  B.  dysenteriae  "Y." 

On  the  Numerical  Relations  of  Bacillus  Dysenteriae. — In  many  of 


46  C.   W.  Duval. 

our  cases  the  colonies  of  dysentery  bacilli  which  grew  upon  the  plates 
were  few  and  not  infrequently  the  bacilli  would  be  obtained  from  one 
or  two  plates  only  of  the  series.  In  other  cases  the  number  of  colonies 
was  much  greater,  and  in  a  few  instances  very  large.  Since  in  our  ex- 
perience the  character  of  the  stool  is  no  reliable  guide  to  the  presence 
or  absence  of  the  bacilli,  every  stool  is  to  be  investigated  exhaustively, 
and  a  second  or  third  specimen  employed  before  closing  the  case  as 
negative.  We  have  at  times  succeeded  by  such  repeated  examinations 
in  retrieving  what  seemed  failures  at  the  outset.  We  have  failed  to 
recover  the  bacillus  from  a  fresh  bloody  discharge  and  succeeded  at  the 
first  attempt  with  a  very  unfavorable  looking  specimen ;  but  as  a  rule  a 
mixture  of  blood  and  mucus  or  a  simple  mucus  specimen  can  be  re- 
garded as  the  most  favorable  material  to  work  with. 

We  failed  in  four  instances  to  obtain  the  dysentery  bacillus  from  cul- 
tures. In  two  of  these  (dispensary  cases)  second  specimens  were  not 
secured  ;  one  of  those  examined  was  a  mixture  of  blood  and  mucus, 
and  hence  should  have  been  favorable,  while  the  other  was  twenty-four 
hours  old  when  received,  and  therefore  unfavorable. 

Several  of  the  specimens  in  our  series  were  of  unusual  interest  and 
we  shall  therefore  give  their  histories  in  some  detail : 

Case  Xo.  44  yielded  a  large,  semi-solid,  green  muco-fecal  stool  in 
which  there  was  no  trace  of  blood.  From  the  mucus  portion  16  plates 
were  prepared.  At  the  end  of  the  first  24  hours  (370  C. )  the  plates 
showed  no  colonies  of  any  sort  to  the  naked  eye ;  at  the  end  of  the 
second  24-hour  period  ( 370  C. )  9  colonies  had  appeared.  All  these 
proved  to  be  colonies  of  B.  dysenteriae.  The  plates  were  now  kept  at 
the  room  temperature  for  about  10  days  and  the  new  colonies  trans- 
planted as  they  appeared.  On  the  fourth  day  24  new  additional  col- 
onies had  developed  on  all  the  plates ;  these  also  proved  to  be  B.  dys- 
enteriae. Xo  other  colonies  appeared  and  hence  the  mucus  of  this 
specimen  is  to  be  regarded  as  containing  the  dysentery  bacillus  in  prac- 
tically pure  culture. 

Case  Xo.  45  yielded  a  large,  soft,  offensive  fecal  stool  containing 
some  mucus  but  no  blood.  Twelve  plates  were  made  from  the  mucus. 
Seventy  colonies  were  transplanted  at  the  first  picking.  60  of  which 
proved  to  be  B.  dysenteriae.  This  transplantation  took  place  18  hours 
after  beginning  incubation,  and  although  the  plates  were  kept  under 
observation  for  10  days  no  more  colonies  of  any  sort  developed.  Had 
the  method  of  "'marking''  and  further  incubation  been  adopted  in  this 
case  negative  results  might  have  been  obtained. 

Case  yi  is  to  be  placed  alongside  case  44  as  respects  the  predom- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  M 

inance  of  the  bacillus  of  dysentery.  Dr.  La  Fetra  prepared  the  plates 
at  the  home  of  the  patient  at  a  distance  from  the  city  from  the  green, 
blood-flecked  mucus  of  the  discharges.  Every  colon}  deep  and  su- 
perficial—which developed  on  the  plates,  numbering  70  in  all,  was 
transplanted  and  all  proved  to  be  growths  of  B.  dysenteriae. 

We  wish  to  place  beside  this  series  of  cases  yielding  the  dysentery  ba- 
cillus in  very  large  numbers  the  following  example  in  which  a  single 
colony  of  the  organism  was  secured  with  great  difficulty  from  a  speci- 
men theoretically  favorable  to  the  isolation  of  the  bacillus.  Case  46  gave 
a  small,  odorless,  blood-stained  mucous  stool  devoid  of  fecal  matter. 
Sixteen  plates  were  prepared  and  after  painstaking  search  and  the 
transplantation  of  many  colonies  a  single  tube  of  the  "Shiga"  type  of 
the  bacillus  was  obtained. 

Finally,  Case  50,  which  gave  a  large  but  offensive  light-yellow, 
blood-flecked  mucus  and  fecal  movement  failed  to  yield  from  the  18 
plates  prepared  a  single  colony  of  B.  dysenteriae. 

Baci'li  Not  Certainly  Identified  as  B.  Dysenteriae.— In  the  course  of 
our  studies  we  encountered  two  bacilli,  which  may  represent  still 
further  variations  of  a  common  bacillus  dysenteriae,  or  may.  perhaps, 
be  entirely  independent  of  that  family  of  organisms.  The  facts  that 
the  variations  which  we  shall  point  out  are  physiological  and  not 
greater  than  those  which  are  already  admitted  in  the  group,  makes  it  at 
least  probable  that  the  bacillus  to  be  described  immediately  is  a  member 
of  the  group. 

In  cases  No.  3  and  6  of  our  series  we  isolated  a  bacillus  which 
agreed  morphologically,  in  staining  properties  and  in  the  usual  cultures 
with  a  typical  control  of  B.  dysenteriae  and  it  agglutinated  in  consider- 
able dilutions  with  anti-dysenteric  serum.  The  chief  differences  noted 
were  its  action  upon  milk  and  upon  lactose-serum-water  fluid. 

The  stool  of  Case  3  was  fecal,  but  contained  some  mucus.  From 
the  mucus  20  plates  were  made,  and  only  two  colonies  of  the  bacilli  to  be 
described  were  isolated.  Besides  B.  coli  communis  many  streptococci 
grew  upon  the  plates.  The  agglutination  tests  were  positive,  1  :8oo 
with  Shiga  A.D.S.,  and  1  :2,ooo  with  Harris  A.D.S.* 

The  bacilli  caused  first  an  acidity  of  the  milk  which  developed  prop- 
erly {i.e.,  within  48  hours),  and  next,  after  a  few  days,  a  return  to  the 
original  hue  (alkali  production).  Xo  further  change  was  noted  for 
5  to  6  days,  when  a  second  acid  change,  more  marked  than  the  first 
and  permanent,  took  place.     The  milk   did  not  coagulate  even  after 


*A.D.S.=Anti-dvsenteric  horse  serum. 


48  C.   W.  Duval. 

many  weeks  of  observation.  That  this  bacillus  attacks  lactose  and  that 
the  second  acidity  is  brought  about  by  this  action  is  rendered  certain  by 
the  lactose-serum-water  medium  which  is  both  acidified  and  coagu- 
lated by  the  bacillus.  As  in  the  case  with  the  true  B.  dysenteriae  it 
acidifies  and  coagulates  dextrose-serum-water.  The  two  colonies  of 
bacilli  from  this  case  which  thus  far  agree  in  their  properties  are  sep- 
arated from  each  other  by  the  employment  of  dextrin-serum-water 
which  is  acidified  and  coagulated  by  one  and  not  by  the  other  culture. 

From  Case  6  a  muco-fecal  stool  was  obtained.  From  the  mucus  14 
plates  were  poured;  from  the  plates  10  colonies  of  a  bacillus  resembling 
B.  dysenteriae  were  isolated.  The  predominating  organisms  develop- 
ing upon  the  plates  were  B.  coli  com.  and  unidentified  motile  bacteria. 
The  ten  colonies  mentioned  were  all  obtained  from  a  single  plate. 
They  agreed  with  the  bacilli  from  Case  3  in  all  respects,  and  like  them 
were  separable  into  two  classes  according  as  they  split  or  failed  to  split 
dextrin  with  the  formation  of  acid. 

The  ability  of  this  bacillus  to  act  upon  lactose  with  acid — but  not 
with  gas — production,  is,  as  would  be  predicted,  constant  and  unaltered 
by  repeated  plating  and  sub-culturing.  It  is  hoped  that  its  properties 
may  be  studied  in  more  detail  later. 

Bacilli  Resembling  B.  Dysenteriae,  but  Certainly  Identified  as  Dis- 
tinct.— We  encountered  in  several  instances  (Cases  Xo.  11,  13,  22,  28, 
38,  46)  bacilli  which  in  early  cultures  may  be  mistaken  for  the  Shiga 
type  of  the  dysentery  bacillus,  although  finally  they  would  be  distin- 
guished from  that  organism.  In  morphology  and  staining  reactions 
and  in  cultures  upon  the  ordinary  fluid  and  solid  nutrient  media  it  can- 
not be  told  from  B.  dysenteriae.  The  agglutinations,  too.  are  positive 
with  horses'  anti-dysenteric  serum,  as  the  bacillus  has  reacted  in  dilu- 
tions of  1  1500  to  1  :iooo.  The  media  which  serve  to  differentiate  the 
bacillus  are  litmus  milk  and  the  Hiss  semi-solid  jelly. 

In  litmus  milk  it  causes  the  primary  acidity,  after  which  there  is  the 
return  to  the  original  color,  but  instead  of  now  going  on  to  a  mild  al- 
kalinity, the  milk  assumes  a  deeper  blue-black  color.  The  first  isola- 
the  lactose-serum-water  medium  which  is  both  acidified  and  coagu- 
lation), but  in  distant  sub-cultures  this  property  is  lost.  The  semi- 
solid jelly  often  brings  out  a  difference  more  quickly,  for  a  part  of  the 
bacilli  of  this  type  are  sufficiently  motile  to  cloud  that  medium,  which 
the  dysentery  bacillus  does  not  do.  .\nother  part  of  the  bacilli,  how- 
ever, is  more  feebly  motile,  or  possibly  non-motile,  and  leaves  the  semi- 
solid medium  unclouded.  With  this  portion  the  differentiation  is 
brought  about  bv  the  litmus  milk  after  a  sufncientlv  long:  observation. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  49 

Th;  serum-water  medium  is  useless  for  this  purpose,  as  all  the 
sugars  except  dextrose  are  unattached,  in  which  the  bacillus  agrees 
with  the  "Shiga"  type  of  the  dysentery  bacillus.  On  the  other  hand,  in 
the  mannite-litmus-agar-agar  the  growth  is  indistinguishable  for 
abcut  a  week,  but  after  this  period  a  cloud-like  spreading  away  from  the 
line  of  stab  may  be  noticed  by  which  the  separation  from  similar  cul- 
tures of  B.  dysenteriae,  which  we  have  never  noticed  spread,  may  be 
made. 

We  have  compared  this  bacillus  with  a  culture  of  B.  fecalis  alka- 
ligenes  and  found  that  the  latter  organism  does  not  act  upon  dextrose, 
which  the  preceding  bacillus  never  fails  to  do. 

Two  rabbits  were  immunized  with  cultures ;  their  serum  agglutinated 
the  bacilli  employed  for  injection  in  dilutions  of  1  :20,000.  With  this 
serum  the  "Shiga"  and  "Flexner-Harris"  types  of  dysentery  bacilli  re- 
acted in  1  125  dilution  for  the  former  and  1  150  for  the  latter,  indicating 
an  absence  of  cross-reactions  with  the  immune  serum  of  the  rabbits- 

Case  11.  Stool  semi-liquid  mucus;  12  plates  prepared;  7  colonies 
of  B.  dysenteriae  isolated.  The  cultures  contained  both  types  of  ba- 
cilli, of  which  5  were  of  the  "Flexner-Harris"  and  2  of  the  "Shiga"' 
type.     The  alkali-producing  bacillus  was  of  the  motile  variety. 

Case  13.  Stool  yellow  mucus  with  flecks  of  blood;  24  plates  made; 
30  colonies  of  B.  dysenteriae  isolated.  Both  types  of  bacilli — 2  of 
"Harris"  and  28  of  "Shiga" — present.  The  alkaline  bacillus  was 
present.     Whether  motile  or  non-motile  variety  has  been  overlooked. 

Case  22.  Semi-liquid  green  mucous  stool;  12  plates  poured;  22  col- 
onies of  "Flexner-Harris"  type  of  dysentery  bacillus  isolated.  Many 
colonies  of  the  non-motile  variety  of  alkaline  bacillus  obtained. 

Case  28.  Muco-fecal  stool ;  20  plates  made ;  7  colonies  of  "Flex- 
ner-Harris" type  of  B.  dysenteriae  picked  off.  Numerous  motile,  al- 
kali-producing bacilli  present. 

Case  38.  '  Green,  muco-purulent  stool;  17  plates  made;  6  colonies  of 
B.  dysenteriae  picked  off;  4  "Flexner-Harris,"  2  "Shiga"  type.  The 
variety  of  the  alkali-forming  bacillus  overlooked. 

Case  46.  Small  stool  of  mucus  containing  blood ;  16  plates  pre- 
pared ;  this  favorable  case  theoretically  yielded,  after  painstaking  search, 
a  single  colony  of  the  "Flexner-Harris"  dysentery  bacillus.  Besides 
this  colon  bacilli,  streptococci,  B.  proteus  and  the  alkali-producing  ba- 
cillus (variety  not  stated)  were  present. 

The  above  cases  briefly  stated,  in  which  the  alkali-producing  bacillus 
was  found,  contained  at  the  same  time  the  true  dysentery  bacillus.  A 
noteworthy  fact  and  one  to  which  we  shall  return  is  that  in  3  of  the 


50  C.   W.  Duval. 

5  cases  both  types  of  the  latter  organism  were  present.  In  view  of  this 
finding  the  appreciation  of  the  extraneous  alkali-forming  bacillus  is  of 
great  importance. 

Single  and  Double  Infection  zvith  Bacillus  Dysenteriae. — We  shall 
for  the  present  denominate  as  single  infection  those  cases  in  which  a 
single  type,  and  as  double  infection  those  cases  in  which  the  two 
types  distinguished  as  "Shiga"  and  "Flexner-Harris"  varieties  are 
found.  An  examination  of  the  table  will  show  at  a  glance  the  great 
preponderance  of  the  "Flexner-Harris"  type  of  bacillus  in  the  cases 
studied  by  us,  which  fact  is  in  keeping  with  Gay  and  Duval's  studies, 
in  regard  to  types,  of  the  bacilli  isolated  by  Duval  and  Bassett  in 
1902.  However,  17  of  the  cases  studied  in  1903  showed  the 
"Shiga"  type  of  bacillus.  Of  these  17  cases  the  organism  was  alone 
present  in  1 1  and  associated  with  the  "Harris"  organism  in  6  instances. 
Hence,  using  our  small  material  of  74  positive  cases  as  a  basis  of  con- 
clusions, we  can  say  that  single  infection  with  the  "Flexner-Harris" 
type  of  bacillus  is  most  common,  that  single  infection  with  the  "Shiga" 
type  of  bacillus  is  far  less  common,  and  that  double  infection  with  both 
organisms  is  least  common  in  the  diarrheal  diseases  of  children. 

Does  Any  Relation  Exist  Between  the  Type  of  Bacillus  and  Charac- 
ter of  the  Dejecta? — Although  it  is  our  experience  that  the  character 
of  the  stool  is  no  certain  indication  of  the  presence  of  dysentery  ba- 
cilli in  isolatable  numbers,  yet  the  stools  in  which  mucus  or  mucus  and 
blood  are  present  in  more  than  perceptible  quantities  rarely  fail  to 
yield  the  organism.  However,  we  have  failed  with  a  given  stool  and 
succeeded  with  a  subsequent  one  of  a  like  character  from  the  same 
patient.  And  while  solid  or  semi-solid  fecal  material  is,  as  a  rule, 
unpromising,  yet  in  rare  instances  the  dysentery  bacillus  has  been  iso- 
lated from  it. 

Since  adult  dysentery  has,  so  far  as  is  at  present  known,  been  asso- 
ciated chiefly  with  the  presence  of  the  "Shiga"  type  of  bacillus,  it 
seemed  to  us  worth  while  to  inquire  whether  the  children  in  whom  that 
type  of  bacillus  was  found  presented  any  peculiarity  of  infection 
worthy  of  notice.  Examination  of  the  records  of  the  stools  from 
which  the  "Shiga"  type  of  bacilli  were  obtained  has  revealed  the  facts 
that  in  6  instances  no  blood  occurred,  in  four  instances  it  was  present 
as  "flecks,"  and  in  only  one  instance  in  more  marked  amounts.  All 
the  stools,  on  the  other  hand,  showed  mucus,  and  except  in  two  in- 
stances in  considerable  quantities.  With  one  or  two  exceptions  feces 
were  admixed  with  the  mucus. 

The  cases  in  which  double  infection  occurred  were  not  distinguish- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  51 

able  so  far  as  the  stool-condition  was  concerned  from  the  cases  of  single 
infection  with  the  "Shiga"  type  of  bacillus.  Blood  was  rarely  present 
in  the  stools  and  never  in  larger  quantity  than  "flecks,"  while  mucus  was 
abundant.  In  about  half  the  cases,  that  is  in  three  instances,  fecal 
matter  was  quite  absent  and  in  two  samples  pus  was  visible  to  the 
naked  eye. 

Since  the  cases  which  we  examined  this  year  were  characterized  by 
far  less  blood  in  the  movements  than  occurred  in  the  series  of  cases 
studied  in  1902  by  Duval  and  Bassett,  the  character  of  the  stools  in  all 
the  infections  may  be  looked  upon  as  in  agreement,  by  which  is  meant 
that  the  severer  cases  in  which  much  mucus  existed  as  well  as  very 
light  infections  in  which  little  mucus  occurred,  arose  in  the  course  of 
all  forms  of  infection,  whether  single  with  either  type  of  the  bacillus 
or  double  with  both  types  of  bacilli. 

Now  that  it  would  appear  as  if  no  distinction  can  be  made  in  the 
degree  of  infection  as  regards  the  type  of  infecting  organism,  the  ques- 
tion arises  as  to  whether  any  relation  exists  between  the  severity  of 
the  lesions  and  the  number  of  dysentery  bacilli  which  can  be  isolated 
from  the  stools.  This  question  has  already  been  answered  by  Duval 
and  Bassett,  who  regarded  cases  in  which  the  movements  consisted 
of  blood  and  mucus  as  most  favorable  to  the  finding  of  B.  dysenteriae. 
An  examination  of  the  table  given  herewith  will  give  our  answer  to 
the  question,  which  is  that  the  presence  of  fecal  matter  in  the  move- 
ments tends  to  reduce  the  number  of  dysentery  bacilli  recovered  from 
the  plates.  But  when  there  is  much  mucus  present  and  the  plating  is 
carried  out  quickly  with  the  fresh  stools,  the  fecal  admixture  is  of  far 
less  importance  in  affecting  the  ultimate  result.  We  are  therefore  led 
to  think  that  intra  vitam  the  mucus  is  the  habitat  of  the  dysentery 
bacillus  and  the  colon  bacillus  is  inhibited  from  a  free  development 
beside  this  organism;  but  outside  the  body  the  latter  organism  may 
quickly  invade  the  mucus  and  overgrow  or  suppress  the  former  ba- 
cillus. That  putrefactive  changes  in  the  intestinal  contents  affect  un- 
favorably the  subsequent  isolation  of  the  bacillus  of  dysentery  is  in- 
dicated by  our  results  with  offensive  stools   (cases  30  and  50). 

Concerning  Bacillus  "Y ." — After  the  description  by  Hiss  and  Russell 
of  a  variety  of  dysentery  bacillus  differing  from  the  "Flexner-Harris" 
type  by  virtue  of  its  inability  to  attack  dextrine,  we  noted  the  cases  in 
which  this  variety  was  present.  By  referring  to  the  table  it  will  be 
seen  that  whereas  the  "Flexner-Harris"  bacillus  occurred  55  times, 
bacillus  "Y"  occurred  12  times  and  in  all  but  one  instance  it  was  associ- 
ated with  the  "Flexner-Harris"  bacillus.    Its  number,  as  indicated  bv  the 


52 


C,   W.  Duval. 


Fermenters 

c/> 

of  Mannit. 

u    .  ^ 

0) 

•0 

8  5  "3 

S  =j  bx 

"3 
0 

_o-5 

"3 

c2 

"5 

1- 

s. 

; 

Brief    Description 

,_«        JO 

rt  1)  p 
u   in   E 

•-    *   3 

.EUZ 

en 

D  S  -X 

D  0  0 

m 

re 

— 1/3 
£5 

(j  — 

of  the   Stool. 

U 

E 

a 

; 

ft 

2 

s 

£ 

fc 

i 

24 

22 

22 

0 

0 

0 

+ 

+ 

Large  mucous  stool. 

2 

24 

46 

46 

0 

0 

0 

+ 

0 

Small  mucous  stool. 

3 
4 
5 
6 

20 

2 

2 

0 

0 

0 

+ 

+ 

Large  muco-fecal. 

28 

47 
1 

47 
1 

0 

0 

0 

+ 

0 

Small  mucous  stool. 

20 

0 

0 

0 

+ 

+ 

Yellow  fecal  stool. 

14 

10 

8 

2 

0 

0 

+ 

+ 

Muco-fecal. 

7 

'3 

4 

2 

0 

2 

0 

+ 

+ 

Brown  semi- solid. 

8 

13 

8 

1 

0 

7 

0 

+ 

0 

bellow  mucus. 

9 

IO 

15 

1 

1 

0 

0 

0 

+ 

+ 

Yellow  mucus. 

20 

39 

39 

0 

0 

0 

+ 

+ 

Yellow  muco-fecal. 

]  i 

12 

7 

5 

0 

2 

0 

+ 

+ 

Muco-fecal. 

12 

15 

20 

20 

0 

0 

0 

+ 

+ 

Semi-liq.  mucus. 

13 

24 

3° 

1 

1 

28 

+ 

+ 

+ 

Green  muco-fecal. 

14 

12 

20 

20 

0 

0 

+ 

+ 

0 

Blood-flecked  mucus. 

15 

20 

1 

0 

0 

1 

+ 

+ 

+ 

Blood-flecked  mucus. 

16 

16 

40 

40 

0 

0 

+ 

+ 

+ 

Yellow  fecal  mass. 

17 

12 

1 

0 

0 

1 

+ 

+ 

+ 

Green   muco-fecal. 

l8 

23 

31 

5 

26 

0 

+ 

+ 

0 

Blood-flecked  mucus. 

!9 

24 

4 

1 

0 

3 

+ 

+ 

+ 

Small  bloody  mucous. 

20 

12 

12 

12 

0 

0 

+    •• 

+ 

+ 

Mucus  and  pus. 

21 

17 

20 

Q 

1 1 

0 

+ 

+ 

+ 

Blood-flecked  mucus. 

22 

12 

22 

22 

0 

0 

+ 

+ 

0 

Blood-flecked  mucus. 

23 

16 

30 

3° 

0 

0 

0 

+ 

+ 

Green    semi-liq.    mucus. 

24 

14 

18 

l8 

0 

0 

0 

+ 

+ 

Yellow  semi-liq.  mucus. 

25 

16 

2 

2 

0 

0 

0 

+ 

+ 

Green  muco-fecal. 

26 

16 

3 

3 

0 

0 

0 

+ 

+ 

Muco-fecal. 

27 

20 

8 

8 

0 

0 

0 

+ 

+ 

Green    muco-fecal. 

28 

20 

7 

7 

0 

0 

0 

+ 

+ 

Muco-fecal. 

29 

20 

13 

13 

0 

0 

0 

+ 

0 

Yellow  mucus. 

3° 

»9 

2 

2 

0 

0 

0 

+ 

+ 

Green   offensive   fecal. 

3l 

15 

3 

2 

1 

0 

0 

+ 

+ 

Yellow   liq.  mass. 

32 

20 

3 

3 

0 

0 

0 

+ 

+ 

Muco-fecal. 

33 

24 

34 

0 

0 

34 

0 

+ 

+ 

Large   liq.    muco-fecal. 

3+ 

12 

2 

1 

1 

0 

0 

+ 

+ 

Green    muco-fecal. 

^5 

22 

22 

22 

0 

0 

+ 

+ 

+ 

Viscid   bloody   mucus. 

36 

12 

3 

0 

0 

3 

0 

+ 

+ 

Large   liq.    muco-fecal. 

37 

21 

41 

41 

0 

0 

0 

+ 

+ 

Green   muco-fecal. 

38 

17 

6 

4 

0 

2 

0 

+ 

+ 

Green    mucus   and    pus. 

39 

»4 

2 

2 

0 

0 

0 

+ 

+ 

Semi-solid  mucous. 

40 

'7 

47 

33 

M 

0 

0 

+ 

+ 

Large  muco-fecal. 

41 

16 

41 

41 

0 

0 

0 

+ 

0 

Mucous  stool. 

42 

16 

18 

18 

0 

0 

+ 

+ 

+ 

Blood-flecked  mucus. 

43 

'7 

45 

0 

0 

45 

0 

+ 

+ 

Yellow   mucus. 

44 

16 

33 

33 

0 

0 

0 

+ 

+ 

Large    muco-fecal. 

45 

12 

60 

60 

0 

0 

0 

+ 

+ 

Large   soft   fecal   stool. 

46 

16 

1 

1 

0 

0 

+ 

+ 

+ 

Mucous  and  bloody. 

47 

29 

25 

5 

20 

0 

0 

+ 

+ 

Light   yellow    feces. 

48 

17 

6 

5 

1 

0 

+ 

+ 

+ 

Green    bloody    muco-fecal. 

49 

18 

1 

1 

0 

0 

0 

+ 

+ 

Watery  brown  and    offensive 

50 

18 

0 

0 

0 

0 

0 

+ 

+ 

Large   offensive    mucous. 

51 

12 

11 

11 

0 

0 

0 

+ 

+ 

Brown    muco-fecal. 

52 

15 

15 

'5 

0 

0 

+ 

+ 

+ 

Blood-flecked  mucus. 

53 

23 

0 

0 

0 

0 

0 

+ 

0 

Yellow   serum. 

54 

12 

23 

23 

0 

0 

0 

+ 

? 

Brown-stained  mucus. 

55 

12 

4 

0 

0 

4 

0 

+ 

+ 

Muco-fecal   and  curdy. 

56 

J4 

2 

0 

0 

2 

0 

+ 

+ 

Green  muco-fecal. 

57 

20 

0 

0 

0 

0 

0 

+ 

0 

Curdy   stool. 

58 

17 

1 

1 

0 

0 

+ 

+ 

? 

Bloody  mucus. 

59 

12 

2 

2 

0 

0 

+ 

+ 

0 

Bloody  mucus. 

60 

14 

1 

1 

0 

0 

0 

+ 

+ 

Green  muco-fecal. 

Studies  of  the  Diarrheal  Diseases  of  Infancy. 


53 


Fermenters 

in 

a; 

of    Mannit. 

D       . 

_       Xi 
rt  u  S 

■a  S3  a 

c  °  rt 

Ik 

s> 

0 

0 

O 
■~C/2 

0 

0 

■Ben 

Brief   Description 
of  the   Stool. 

01 

u 

>-       U3 

oi 

3  <D 

8  « 

•SuZ 

aj 

pq 

0 

0  0  ~ 

^ 

u£ 

u 

eu 

Q 

: 

pq 

2 

pq 

s 

fa 

61 

12 

18 

0 

18 

0 

0 

+ 

? 

Creamy   pus  and  mucus. 

62 

12 

3 

3 

0 

0 

0 

+ 

? 

Semi-solid   green   mucus. 

63 

12 

2 

2 

0 

0 

0 

+ 

0 

Bloody   mucus. 

64 

16 

0 

0 

0 

0 

+ 

+ 

> 

Green    mucus. 

6s 

12 

2 

2 

0 

0 

0 

+ 

0 

Yellow  serum. 

66 

12 

1 

0 

0 

1 

+ 

+ 

? 

Bloody  mucus. 

67 

24 

2 

2 

0 

0 

0 

+ 

0 

Yellow   curdy    mass. 

63 

14 

1 

0 

0 

1 

+ 

+ 

0 

Mucus   with   blood   fleck. 

69 

12 

18 

18 

0 

0 

+ 

+ 

0 

Blood-flecked    mucus. 

70 

12 

12 

12 

0 

0 

0 

+ 

? 

Mucosa  scraping. 

7i 

6 

70 

70 

0 

0 

+ 

+ 

0 

Blood-flecked   mucus. 

72 

24 

0 

0 

0 

0 

+ 

+ 

0 

Bloody   mucus. 

73 

6 

1 

0 

0 

1 

+ 

+ 

? 

Blood-flecked   mucus. 

74 

16 

1 

1 

0 

0 

0 

+ 

+ 

Brown    muco-fecal. 

75 

15 

3 

2 

1 

0 

+ 

+ 

+ 

Muco-fecal,  blood  flecked. 

76 

J9 

8 

0 

0 

8 

o 

+ 

+ 

Green  muco-fecal. 

77 

20 

8 

8 

0 

0 

3 

+ 

0 

Yellow  mucus  and  pus. 

78 

24 

3 

3 

0 

0 

O 

+ 

+ 

Green    muco-fecal. 

79 

22 

5 

2 

3 

0 

O 

+ 

+ 

Muco-fecal. 

Notes  : 
Nos.  1  to  67  inclusive  are  the  cases  obtained  from  Vanderbilt  Clinic. 

68  to  72       "         "       "       "  "  "      Post  Graduate  Hospital. 

73  to  75       "         "       "       "     sent  by  Dr.  La  Fetra. 

76  is  a  private  case  of  Dr.  Larkin  (autopsy). 

77  is  a  case  from  the  Roosevelt  Hospital. 

78  and  79  are  private  cases  sent  by  Dr.  Schwerdtfeger. 
Numbers  50,  53,  57,  64  and  72  are  the  negative  cases. 

Numbers  7,  8,  11,  13,  19  and  38   are   cases   in    which    both  types   ("  Flexner-Harris  "   and 

"  Shiga  ")  were  recovered  from  the  stool. 
Eleven  (11)  cases  contained  the    '  Shiga  "  type  only. 
Fifty-five  (55)  cases     "  "     "Flexner-Harris"   type   either   alone   or   associated    with 

Bacillus  "Y." 
Six  (6)  cases  "  "     "  Shiga  "  and  "  Flexner-Harris  "  types  in  association. 

One([)  case  "  "     Bacillus   "Y"  only. 


cultures  varied  considerably,  and  they  bore  no  fixed  relation  to  the 
"Flexner-Harris"  organism.  While  it  might  form  but  a  fraction  of 
the  entire  number  of  dysentery  colonies,  it  might  again  be  the  pre- 
dominating bacillus. 

Hie  "Flexner-Harris"  Bacillus  in  Normal  Stools. — In  view  of  the 
wide  distribution  of  B.  dysenteriae  in  the  intestinal  diseases  of  children 
a  search  was  made  to  ascertain  whether  they  might  possiblv  be  pres- 
ent in  the  intestine  of  normal  children.  For  this  purpose  we  employed 
the  stools  of  normal  milk-fed   infants.     The  procedure   was   as    fol- 


54  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

lows  :  The  rectum  was  first  irrigated  after  which  a  dose  of  castor  oil 
and  rhubarb  was  administered.  The  first  two  free  movements  were 
examined.  The  method  was  to  use  the  usual  technique  with  the  first 
stool,  while  from  the  second  one  from  3  to  6  drops  of  the  bouillon 
suspension  were  carried  into  the  plates.  This  modification  was  neces- 
sary to  obtain  plates  with  a  fair  number  of  colonies.  From  each  case 
50  to  100  plates  were  procured  and  several  hundred  colonies  (up  to 
300)  transplanted  to  the  semi-solid  jelly.  By  this  means  we  succeeded 
in  isolating-  a  few  colonies  of  the  "Flexner-Harris"  bacillus  from  the 
stools  of  two  infants  who  were  in  perfect  health. 


REPORT  OF  MARTHA   WOLLSTEIN,   M.D.,   ASSISTED    BY 
GRACE  DEWEY,  M.D. 

From  the  Laboratory  of  the  Babies'    Hospital,  New  York. 

During  the  three  months  extending  from  June  15th  to  September 
15th  there  were  studied  by  us  62  cases  of  diarrhea,  which  were  ex- 
amined with  respect  to  the  presence  of  Bacillus  of  Dysentery  (Shiga) 
in  the  dejecta  and  the  intestinal  mucosa  after  death.  The  materials  of 
our  study  were  obtained  from  the  Babies'  Hospital,  the  N.  Y.  Found- 
ling Hospital  and  in  one  instance  from  Dr.  E.  L.  Coolidge.  The  chil- 
dren varied  in  age  from  six  weeks  to  two  years.  , 

The  specimens  from  the  stools  were  taken  in  the  following  way : 
At  the  Babies'  Hospital,  when  a  case  had  been  diagnosed  as  "diar- 
rhea" in  the  ward,  a  characteristic  stool  was  sent  to  the  laboratory  as 
soon  as  passed,  and  plates  were  poured  at  once.  At  the  Foundling 
Hospital  the  cases  in  the  ward  for  intestinal  diseases  were  visited 
every  morning,  and  suspensions  from  the  fresh  stools  made  in  peptone 
water.  These  were  carried  to  the  laboratory  and  plated  within  half 
an  hour.  The  children  in  the  latter  institution  were  more  severely 
ill  and  the  mortality  rate  was  higher  than  was  the  case  at  the  Babies' 
Hospital.  This  may  be  partly  explained  by  the  fact  that,  as  the  babies 
are  boarded  out  in  the  tenements  to  paid  nurses,  they  are  returned 
to  the  hospital  only  when  they  become  very  ill.  At  the  Babies'  Hospital 
almost  every  case  of  diarrhea  was  studied. 

Of  the  62  cases  the  dysentery  bacillus  was  isolated  in  48  instances, 
that  is  78  per  cent,  of  all  cases  were  positive  for  the  bacillus.  Numeric- 
ally the  cases  occurred  as  follows :  Babies'  Hospital,  33 ;  Foundling 
Hospital,  28;  private  practice,  1.  Among  the  33  cases  studied  from 
the  Babies'  Hospital  22,  or  67  per  cent.,  gave  positive  results;  and  of 
the  28  cases  studied  at  the  Foundling  Hospital  25,  or  89  per  cent.,  gave 
positive  results.  The  mortality  of  the  cases  yielding  the  dvsenterv 
bacillus  was  55  per  cent,  at  the  Babies'  Hospital  and  78  per  cent,  at 
the  Foundling  Hospital. 

The  discharges  varied  considerably.  Blood  was  present  in  a  little 
more  than  one-third  of  all  cases  studied,  namely  in  22  instances  and 


56  Martha  Wollstein. 

among  these  the  dysentery  bacillus  was  found  19  times.  Mucus  in  mod- 
erate or  large  quantity,  in  the  absence  of  blood,  was  noted  in  23  cases  : 
among  these  20  showed  the  presence  of  the  bacillus.  Mucus  in  small 
quantity,  in  the  absence  of  blood,  was  present  in  17  cases  of  which 
o,  gave  the  dysentery  bacillus  in  culture.  From  this  statement  it  will 
appear  that  movements  containing  much  mucus  are  favorable  for  ob- 
taining the  bacillus,  irrespective  of  the  presence  of  blood  in  the  dis- 
charges. 

On  the  whole,  the  number  of  colonies  of  the  dysentery  ba- 
cillus present  on  the  plates  was  not  very  numerous,  though  in  one 
case  they  were  almost  the  only  variety  present.  In  the  case? 
containing  much  mucus,  with  or  without  blood,  Bacillus  dysen- 
teriae  was  often  found  quite  readily  at  the  first  "fishing";  but,  when 
the  case  came  under  observation  comparatively  late  in  the  disease 
(after  the  second  week),  it  was  hard  to  find  even  in  stools  contain- 
ing blood. 

Stools  with  small  amounts  of  mucus,  no  blood,  and  a  large  amount 
of  fecal  matter,  often  necessitated  fishings  of  very  large  numbers  of 
colonies  on  successive  days  in  order  to  find  any  dysentery  bacilli,  and 
the  result  on  several  occasions  was  but  a  single  positive  tube.  An 
interesting  point  in  this  connection  is  that  when  such  stools  occur 
at  the  onset  of  a  subsequently  severe  attack,  Bacillus  dysenteriae  is 
found  in  them  in  comparatively  large  numbers,  and  increases  as  the 
.stools  become  more  mucous  or  bloody  in  character.  On  the  other 
hand,  if  the  attack  is  simply  one  of  mild  intestinal  disturbance,  with- 
out the  appearance  of  any  larger  quantity  of  mucus  at  any  time,  the 
organisms  'are  found  in  very  small  numbers  or  not  at  all.  The  same 
is  true  of  those  fecal  stools  containing  a  very  small  quantity  of  mucus 
which  occur  during  the  latter  part  of  an  attack  of  dysentery,  or  during 
convalescence.  A  good  clinical  history  is  important  for  the  determi- 
nation of  these  points. 

The  number  of  colonies  of  the  dysentery  bacillus  transplanted,  which 
represents  the  number  of  cultures  obtained  from  a  given  case,  varied 
from  1  to  25.  All  the  colonies  agreed  in  behaving  on  the  litmus- 
mannite-agar  medium  as  does  the  "Flexner-Harris"  type  of  bacillus.  In 
no  instance  was  a  colony  of  the  "Shiga"  type  discovered. 

The  agglutination  tests  were  made  with  the  antidysenteric  serum 
prepared  in  the  horse  and  supplied  by  Dr.  Flexner.  The  positive  re- 
actions were  obtained  with  "Harris"  serum  in  dilutions  up  to  1  13,000 
and  with  the  "Shiga"  serum  up  to   1  400.     There  were  some  varia- 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


57 


tions  among  the  individuals  isolated,  in  that  certain  of  them  proved 
relatively  poor  agglutinators. 

Blood  in  sufficient  quantity  to  suffice  as  a  test  for  agglutination  was 
obtained  from  7  children  giving  positive  and  2  giving  negative  bac- 
teriological results  • 

/.  Positive  Cases. 

3d     day,  positive  in  dilution  of  1-200,     1   case 


6th 

6th 
7th 
2nd 
4th 
10th 


negative 


I-IOO, 

1-40, 

1-200, 

1-50, 

1-50, 

1-50, 


II.  Negative  Cases. 

5th    day,  negative  in  dilution  of  1-50, 
6th      "  "         "         "         "    1-50, 


1  case 
1     " 


Our  experience  in  examining  stools  and  scrapings  from  the  intestinal 
mucosa  in  the  same  case  convinced  us  that  the  dysentery  organisms  are 
at  times  more  richly  present  in  the  intestine  than  in  the  discharges. 
Thus  case  51  showed  a  small  number  of  colonies  in  the  stool  and  a 
large  number  in  scrapings  made  from  the  rectum  after  death.  Case  25 
showed  a  moderately  large  number  of  colonies  in  the  stool  (24)  and 
a  much  greater  number  in  plates  made  from  scrapings  of  the  mucosa 
of  the  intestine.  Case  29  was  a  failure  until  scrapings  from  the  colic 
mucous  membrane  were  examined.  On  the  other  hand  three  cases 
(5,  6,  18)  were  negative  both  in  respect  to  stools  and  scrapings.  Case 
5  was  first  examined  June  18.  The  stool  was  small  and  thin  and 
contained  a  small  amount  of  mucus.  The  autopsy  was  performed  on 
July  15th  and  scrapings  taken  from  the  ileum  and  colon.  Case  6 
gave  a  stool  containing  a  small  quantity  of  mucus ;  the  rectum  was 
scraped  after  death.  Case  18,  stool  showed  very  small  quantity  of 
mucus ;  rectum  scraped  after  death. 

We  observed  one  instance  of  terminal  infection  in  which  a  large 
number  of  colonies  of  the  dysentery  bacillus  developed  on  the  plates. 
The  case  (13)  was  that  of  a  child  of  5  months  who  was  brought  to  the 
Babies'  Hospital  suffering  from  nephritis.  Bloody  discharges  began 
10  days  after  the  child  had  entered  the  hospital.  The  case  terminated 
fatally ;  no  autopsy  was  permitted. 

In  one  instance   (Case  61)   we  obtained  from  a  stool  containing  a 


Martha  Wollstein. 


V 

Type  of 

J2 

"U 

Colonies. 

"o 
0 

3 
2 

oS 

£r  2 "° 

:, 

. 

"0 
c  2 

c2 

in 

Brief  Description 

Termination 

1-  tn 

<u'E  H 

.2 

ca 

•sc/) 

•-C/3 

c 

of  Stool.                     of  Case. 

u   en 

So 

13 

c  — -5 

v  0  O 

en 

•0 
0 
0 

3 
3 

in 

u 
V 

O 

2 

a 

: 

' 

m 

s 

ta 

i 

6 

16 

All 

0 

+ 

+ 

+ 

Thin  green                             ,  Death. 

2 

6 

4 

All 

0 

+ 

+ 

+ 

Yellow,  small                        'Death. 

3 
4 

5 

6 

3 

All 

0 

+ 

+ 

+ 

Moderately  large  green        Not  stated. 

5 

0 

0 

0 

0 

+ 

+ 

Small,  green                          Not  stated. 

15 

0 

0 

0 

0 

+ 

+ 

Small,    green  ;   little   mu-' Death. 

cus;  much  feces 

6 

10 

0 

0 

0 

0 

+ 

+ 

Small,      grayish-green  ;  Death, 
little  mucus. 

7 

6 

0 

0 

0 

+ 

+ 

+ 

Large,      yellow     fecal  ;i  Not  stated. 

specks    of  blood;   little 

mucus 

8 

4 

4 

All 

0 

+ 

+ 

+ 

Large,  green                        j  Not  stated. 

9 

4 

3 

All 

0 

+ 

+ 

+ 

Small,   thin,    with    much! Not  stated. 

mucus    and    streaks   of; 

blood 

10 

5 

3 

All 

0 

+ 

+ 

+ 

Large,  with  much  mucus 
and    specks   of    blood, 

Not  stated. 

feces 

ii 

7 

2 

All 

0 

0 

+ 

+ 

Large,  thin,    green,   with! Death, 
feces  and    much  mucusl 

12 

2 

7 

All 

0 

+ 

+ 

+ 

Small,     with    mod.    mu-i  Not  stated, 
cus  and  streaks  of  blood 

13 

3 

18 

All 

0 

+ 

+ 

+ 

Small,  chiefly   blood   and  Death. 

mucus 

14 

4 

6 

All 

0 

+ 

+ 

+ 

Small,   green,    with  much 

Death. 

mucus   and    streaks    of 

blood 

15 

8 

3 

All 

0 

0 

+ 

+ 

Large,  white   and  green, 
much  mucus 

Not  stated. 

l6 

4 

18 

All 

0 

+ 

+ 

0 

Small;  blood  and  mucus 

Recovery. 

17 

16 

2 

All 

0 

0 

+ 

+ 

Large,  thin,  green-brown, 
much    mucus 

Not  stated. 

18 

12 

0 

0 

0 

0 

+ 

+ 

Large,  green  ;    very   little 
mucus 

Death. 

x9 

9 

0 

0 

0 

0 

+ 

+ 

Large,  green  ;    very  little 

Death. 

mucus 

20 

6 

7 

All 

0 

+ 

+ 

+ 

Green  ;  much  feces,  littlei  Recovered, 
blood   and   mucus 

21 

12 

2 

All 

0 

0 

+ 

+ 

Small,  yellow  ;   mod.  mu-'Not  stated, 
cus 

22 

8 

0 

0 

0 

0 

+ 

+ 

Green;   much   feces,  little  Not  stated, 
mucus 

23 

12 

5 

All 

0 

+ 

+ 

+ 

Green;  mod.  mucus,  littlejDeath. 
blood 

24 

10 

0 

0 

0 

0 

+ 

+ 

Large,  green  ;  fecal,  little  Recovered, 
mucus 

25 

14 

24 

All 

0 

0 

+ 

+ 

Small,  green;  mod.  mucusl  Death. 

26 

6 

6 

All 

0 

0 

+ 

+ 

Large,  green;   fecal,  little! Recovered, 
mucus 

27 

10 

1 

All 

0 

+ 

+ 

+ 

Small,  green ;  mod.  mucus,  Not  stated, 
streaks  of  blood 

28 

7 

0 

0 

0 

0 
0 

+ 

.  + 

Thin,  green  and   yellow  ;i  Recovered, 
much  feces;  little  mucus! 

29 

10 

3 

All 

0 

+ 

+ 

Thin,    green    and  yellow; 
much  feces;  little  mucus 

Death. 

*3° 

10 

0 

0 

0 

0 

+. 

+ 

Dark   green ;    much   feces 
and  mucus 

Recovered. 

31 

9 

4 

All 

0 

0 

+ 

+ 

Large  green ;   much   feces 
and  mucus 

Death. 

32 

4 

6 

All 

0 

0 

+ 

+ 

Large,  thin,  green  ;  much 

Not  stated. 

feces,  little  mucus 

*  Diarrhea  followed  eating  of  sausage  and  lasted  five  days. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


59 


u 

Type  of 

-i= 

■a 

1-  — 1    <D 

Colonies. 

c  0 

s  0 

"o 

O 

■Si 

Brief  Description 

3 

=  . 

- 

Termination 

o    < 
•-  rt 
■Su 

■213 

2  c  -s 

c  0  rt 

S  "o  c 

U 
U 

ns 

s? 

IS 

'Si 

-a 
0 
0 

3 

u 

3 

1) 

V 

of  Stool.                     of  Case. 

U 

2 

Q 

"- 

- 

5 

*3 

ta 

35 

7 

10 

All 

0 

0 

+ 

+ 

Thin,  green;  much    feces,  Death, 
little  mucus. 

.34 

4 

3 

All 

0 

0 

+ 

+ 

Small   green;    little    feces  Not  stated. 

and  mucus 

35 

10 

8 

All 

0 

0 

+ 

+ 

Small,    green,    yellow; 
mod.  mucus 

Not  stated. 

36 

12 

3 

All 

0 

0 

+ 

+ 

Large,  thin,  green  ;  mod. 
mucus 

Not  stated. 

37 

8 

4 

All 

0 

0 

+ 

+ 

Small,    green;   mod.    mu- 
cus 

Not  stated. 

3* 

6 

7 

All 

0 

0 

+ 

4- 

Small,  green;  little  mucus 

Recovered. 

39 

4 

5 

All 

0 

0 

+ 

+ 

Large,  green ;    much   mu- 
cus, little  feces 

Not  stated. 

40 

M 

0 

0 

0 

0 

+ 

+ 

Yellow  and  green;    much 
feces,  little  mucus 

Death. 

41 

10 

1 

All 

0  • 

+ 

+ 

+ 

Green;    much     mucus, 
speck  of  blood 

Not  stated. 

42 

6 

1 

All 

0 

+ 

+ 

4- 

Thin,  green;  much  mucus, 
flecks  of  blood 

Not  stated. 

**43 

18 

4 

All 

0 

0 

+ 

+ 

Small,  green;  little  mucus, 
feces 

Not  stated. 

44 

5 

6 

All 

0 

0 

+ 

+ 

Green;  much    mucus  and 
feces 

Death. 

45 

16 

2 

All 

0 

0 

+ 

+ 

Large,  brown;    mod.  mu- 
cus and  feces 

Not  stated. 

46 

16 

3 

All 

0 

0 

+ 

+ 

Large,    green;  much  mu- 
eus,  mod.  feces 

Not  stated. 

47 

10 

6 

All 

0 

0 

+ 

+ 

Large,  brown;  mod.  mu- 
cus, mod.  feces 

Not  stated. 

48 

9 

2 

All 

0 

0 

+ 

+ 

Small,  yellow;    much  mu- 
cus and  feces 

Not  stated. 

49 

'4 

1 

All 

0 

0 

+ 

+ 

Green  ;  fecal,  little  mucus 

Death. 

50 

6 

1 

All 

0 

0 

+ 

+ 

Small,  thin,  green;    mod. 
mucus  and  feces 

Not  stated. 

5' 

18 

3 

All 

0 

0 

+ 

+ 

Thin,  green;  much  mucus 
and  feces 

Death. 

52 

10 

3 

All 

0 

0 

+ 

+ 

Large  green;  much  mucus 
and  little  feces 

Not  stated. 

53 

5 

3 

All 

0 

— 



— 

Death. 

54 

4 

3 

All 

0 

0 

+ 

+ 

Small,    yellowish    green  ; 
mod.  mucus  and  feces 

Not  stated. 

55 

5 

3 

All 

0 

+ 

+ 

+ 

Small,     colorless  ;     much 
mucus,  streaks  of  blood, 
little  feces 

Not  stated. 

56 

2 

8 

All 

0 

0 

+ 

+ 

Small,  green;    much  mu- 
cus, mod.  feces 

Not  stated. 

57 

18 

2 

All 

0 

0 

+ 

4- 

Small,    greenish;  little 
mucus  and  feces 

Not  stated. 

58 

12 

3 

All 

0 

+ 

+ 

4- 

Large,  yellow;  much  mu- 
cus, few  streaks   blood, 
mod.  feces 

Not  stated. 

59 

3 

0 

0 

0 

+ 

+ 

+ 

Small,  green  ;   mod.    mu- 
cus,   little      feces,     fetv 
streaks  of  blood 

Death. 

to 

8 

25 

All 

0 

— 



— 



Death. 

61 

10 

0 

0 

0 

0 

4- 

4- 

Large,    yellowish    brown  ; 
mod.  mucus,  much  feces 

Not  stated. 

62 

12 

0 

0 

0 

+ 

+ 

4- 

Thin,  yellow;    much   mu- 
cus,   streaks    of    blood, 
little  feces 

Not  stated. 

**Sets  of  plates  made  two  weeks  previously  failed  to  yield  B.  dysenterias. 
Cases  55  and  60. — Used  scrapings  of  intestinal  mucosa  obtained  at  autopsy. 
Case  61. — Non-motile,  alkali-producing  bacillus  isolated. 


60  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

moderate  quantity  of  mucus  a  non-motile  bacillus  which  conducted  it- 
self in  a  manner  similar  to  the  "Shiga"  type  of  dysentery  bacillus,  but 
there  was  strong  alkali  formation  in  litmus  milk  after  a  primary  acid 
production.  The  bacillus  did  not  agglutinate  with  "Shiga"  antidysen- 
teric  serum. 

The  foregoing  table  gives  in  numerical  order  the  cases  which  we 
studied  and  the  results  of  the  bacteriological  examination. 


REPORT  OF  FREDERICK  P.  GAY,  M.D.,  ASSISTED  BY 
E.  McD.  STANTON,  M.D. 

The  stools  from  cases  of  infantile  diarrhea  which  have  come  into 
our  hands  for  bacteriological  investigation  during  the  months  of  June, 
July,  August  and  September — our  working  period  having  extended 
from  the  end  of  June  to  the  middle  of  September — were  obtained  from 
two  sources.  The  larger  number  of  specimens  was  sent  in  by  the  New 
York  Health  Department,  the  cases  from  which  they  had  been  obtained 
being  observed  clinically  and  the  specimens  collected  by  the  district 
medical  inspectors  in  their  rounds  of  the  tenement  districts.  The 
smaller  number  of  specimens  was  obtained  from  the  children's  wards 
of  Bellevue  Hospital  through  the  courtesy  of  Drs.  Mabon  and  Xorrie 
and  the  resident  staff.  The  examination  of  the  collected  material  was 
carried  out  in  the  Bacteriological  Laboratory  of  the  New  York  Uni- 
versity and  Bellevue  Hospital  Medical  College.  We  wish  to  thank  the 
many  persons  who  directly  and  indirectly  assisted  us  for  their  interest 
and  courtesies. 

Owing  to  the  nature  of  the  circumstances  affecting  the  material 
with  which  we  operated,  the  most  satisfactory  bacteriological  results 
were  obtained  with  the  specimens  supplied  from  the  wards  of  Belle- 
vue Hospital.  From  a  clinical  standpoint  the  cases  yielding  the  dejecta 
were  similar  in  the  hospital  and  the  tenement  districts,  with  the  pos- 
sible difference  that  the  cases  which  found  their  way  into  the  hos- 
pital were  often  of  longer  duration  than  in  the  latter  quarter.  But 
the  most  important  difference,  so  far  as  our  studies  were  concerned, 
consisted  in  the  fact  that  complete  fresh  stools  could  be  obtained  from 
the  hospital  while,  through  the  unavoidable  nature  of  the  situation, 
we  had  to  content  ourselves  with  small  portions  of  mucus,  etc.,  which 
were  chosen  hurriedly  by  the  medical  inspectors  and  sent  us  sus- 
pended in  normal  saline  solution  and  which  reached  us  some  hours 
often  after  being  collected.  Seeing  that  this  latter  material  was  obtained 
from  napkins  which  had  not  been  sterilized  and  had  often  been  kept 
under  careless  conditions  for  hours,  it  was,  theoretically,  unpromis- 
ing for  the  purposes  of  our  investigation.  It  is,  therefore,  not  surpris- 
ing that  the  specimens  from  a  large  number  of  the  cases  of  diarrhea 
occurring  in  the  tenement  district  were  found  to  be  grossly  contami- 
nated with  air  and  other  foreign  bacteria. 


62  Frederick  P.  Gay. 

The  material  from  Bellevue  Hospital,  on  the  other  hand,  was  re- 
ceived on  sterile  pads  almost  immediately  after  its  passage  and  the 
plates  made  from  it  were  completed  frequently  within  half  an  hour 
after  the  movement  had  taken  place.  Besides  this  we  could  observe 
and  record  the  character  of  the  stool  and  make  a  deliberate  selection 
of  those  portions  which  offered  the  best  opportunities  for  successful 
bacteriological  study. 

The  method  which  we  pursued  in  separating  the  bacillus  of  dysen- 
tery was  essentially  that  described  by  Vedder  and  Duval.  Several 
suspensions  were  made  of  the  mucus  from  various  parts  of  the  stool 
and  from  these  suspensions  transfers  of  a  varying  number  of  loops 
were  made  to  fluid  agar-agar  which  was  acid  1.5  per  cent,  to  phenol- 
phthalein.  Frequently  the  mucus  particles  were  washed  in  sterile  salt 
solution  before  suspension  to  remove  the  excess  of  colon  bacilli  which 
are  contained  in  the  fecal  part  of  the  stool.  On  an  average  about  20 
agar-agar  plates  were  made ;  but  in  some  unpromising  cases  as  many 
as  thirty  or  forty  were  prepared.  In  general  the  most  satisfactory 
plates  were  found  to  be  the  rather  thickly  seeded  ones;  e.g.,  those  con- 
taining from  200  to  300  colonies.  After  the  lapse  of  the  twenty-four 
hour  incubation  period  and  the  marking  of  the  superficial  colonies, 
subsequently  developing  surface  colonies  of  the  colon  bacillus  type 
were  taken  directly  into  1  per  cent,  glucose  agar,  or,  better  still,  into 
Hiss'  semi-solid  gelatine-agar  medium  which  has  the  advantage  of 
showing  motility  and  gas  production  within  a  few  hours  after  inocula- 
tion and  incubation.  All  non-motile,  non-gas-forming  bacilli  were 
then  grown  in  litmus  milk  and  such  of  them  as  showed  the  slight  acid 
production  in  24  hours,  characteristic  of  the  growths  of  B.  dysenteriae, 
were  tested  for  agglutination  with  two  antidysenteric  horse's  sera 
representing  the  "Shiga"  and  the  "Flexner-Harris"  strains  of  the 
bacillus  of  dysentery.  The  dysentery  bacilli  agglutinate  with  both 
sera,  but  relatively  better  with  the  serum  of  the  type  to  which  the 
bacillus  belongs. 

The  stools  which  yielded  B.  dysenteriae  did  so  readily,  as  a  rule,  on 
the  second  or  third  "picking,"  but  we  met  with  a  few  stools  in  which 
we  succeeded  only  after  three  or  four  "pickings"  in  obtaining  a  single 
colony  of  the  organism.  The  small  proportion  of  dysentery  bacilli  oc- 
curring in  the  latter  stools  may  be  gathered  from  the  fact  that  as  many 
as  100  to  200  colonies  were  at  times  transplanted  in  order  to  obtain 
this  imperfect  result. 

Of  the  microorganisms  growing  in  cultures  the  ones  frequently  met 
with — excluding  B.  dysenteriae — in  our  plates  were  B.  coli  communis, 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  63 

B.  fecalis  alkaligenes,  B.  acidi  lactici,  and  the  streptococcus.  A  few 
specimens  which  contained  large  numbers  of  streptococci  failed  to 
yield  us  the  dysentery  bacillus. 

Several  bacilli  of  the  colon  group  and  certain  bacilli  resembling  B. 
fecalis  alkaligenes  were  encountered  which  gave  positive  agglutination 
sometimes  with  one,  sometimes  with  the  other  of  the  anti-dysenteric 
sera  of  the  horse ;  but  we  met  with  no  organism  except  the  dysentery 
bacillus  which  reacted  to  both  types  of  serum. 

We  were  successful  in  recovering  the  dysentery  bacillus  from  20 
cases  of  infantile  diarrhea.  Of  the  20  cases  18  contained  organisms  of 
the  "Flexner-Harris"  type  and  2  organisms  of  the  "Shiga"  type.  In 
no  instance  were  the  two  types  of  organism  isolated  from  the  same 
case. 

In  several  instances  the  freshly  isolated  cultures  of  B.  dysenteriae 
failed  to  agglutinate  with  the  anti-dysenteric  sera;  but  these  cultures 
all  reacted  positively  after  repeated  sub-culturing. 

We  met  with  certain  cultures  which  resemble  the  dysentery  bacil- 
lus in  all  respects,  but  which  behaved  in  a  non-characteristic  manner 
upon  litmus-milk.  These  cultures  produced  the  initial  acidity  and 
returned  the  color  of  the  milk  to  that  of  the  control.  But  later  they 
gave  rise  to  a  second  acid-production  which  was  permanent.  We 
have  not  investigated  farther,  because  of  lack  of  time,  the  finer  points 
of  distinction  between  this  organism  and  the  bacillus  of  dysentery. 

MATERIAL    SUPPLIED    BY    NEW    YORK    HEALTH    DEPARTMENT. 

Of  the  28  stools  examined  from  this  source  the  bacillus  of  dysentery 
was  isolated  in  7  instances  or  in  25  per  cent.  We  have  tabulated  the 
cases  from  which  the  specimens  were  obtained  with  reference  to  the 
reported  nature  of  the  stools  : 

Of  12  stools  showing  little  mucus  and  no  blood  two  (2)  gave  B. 
dysenteriae. 

Of  12  stools  showing  moderate  quantities  of  mucus  and  no  blood  five 
(5)  gave  B.  dysenteriae. 

Of  4  stools  showing  large  quantities  of  mucus  and  some  blood  none 
gave  B.  dysenteriae. 

At  the  first  glance  there  is  something  contradictory  in  these  results, 
for  it  has  been  stated  by  Duval  and  Bassett  that  the  stools  in  which 
blood  and  mucus  were  contained  most  easily  yield  B.  dysenteriae  in 
cultures.  The  reason  for  this  unexpected  result  becomes  evident  when 
we  look  at  the  contaminations  which  were  met  with  in  many  of  this 


64  Frederick  P.   Gay. 

class  of  cases  and  which  are  to  be  ascribed  to  the  unfavorable  con- 
ditions under  which  the  collection  of  the  specimens  was  made. 

MATERIAL  SUPPLIED  BY  BELLEVUE   HCSPITAL. 

Of  the  20  cases  examined  from  this  source  the  bacillus  of  dysentery 
was  found  in  13  or  in  65  per  cent.  A  tabulation  of  the  cases  and  re- 
sults follow : 

Of  1  stool  showing  little  mucus  and  no  blood  no  successful  result. 

Of  3  stools  showing-  little  mucus  and  blood  three  ( 3 )  gave  B.  dysen- 
teriae. 

Of  5  stools  showing  moderate  quantity  of  mucus  and  no  blood  five 
(5)  gave  B.  dysenteriae. 

Of  6  stools  showing  large  quantity  of  mucus  and  no  blood  three  (3) 
give   B.   dysenteriae. 

Of  5  stools  showing  large  quantity  of  mucus  and  some  blood  two 
(2)  gave  B.  dysenteriae. 

Our  results  were  assisted  in  this  group  of  cases  by  the  fact  that 
it  was  often  possible  to  secure  a  second  or  third  specimen  of  the  dis- 
charges from  a  given  case ;  and  thus  it  happened  that  after  failure  with 
the  first  specimen  a  subsequent  one,  presenting  the  same  naked-eye 
appearance  as  the  first,  would  yield  B.  dysenteriae.  In  several  of  the 
negative  cases  unusual  conditions  prevailed  which  possibly  accounted, 
in  part,  for  the  failures.  In  one  case  B.  pyocyaneus  overgrew  the  plate 
and  suppressed  other  organisms ;  and  in  another  B.  proteus  behaved  in 
the  same  manner.  One  of  the  stools  was  well  formed,  two  were  watery 
with  a  trace  only  of  mucus,  and  two  stools  contained  enormous  numbers 
of   streptococci. 

Autopsies  were  held  on  five  of  the  fatal  cases.  In  one  case  showing 
generalized  tuberculosis  the  colon  showed  no  lesions  although  the  ba- 
cillus of  dysentery  was  obtained  during  life  from  the  discharges;  in 
two  instances  the  colon  was  congested  and  showed  hemorrhagic  points  ; 
two  cases  presented  extensive  ulcerative  colitis.  In  the  last  two  cases 
the  ileum  showed  ulcers  in  the  one  and  the  base  of  the  appendix  ulcera- 
tion and  gangrene  in  the  other.  Cultures  made  from  the  colon  of  the 
last  two  cases  gave  B.  dysenteriae. 

Very  few  opportunities  were  presented  for  the  study  of  the  agglutina- 
tive power  over  dysentery  bacilli  of  the  blood  of  infants  ill  of  diarrhea. 
The  very  few  specimens  of  blood  which  we  tested  reacted  variously — 
some  positively  in  dilutions  up  to  1  :20,  some  negatively  in  dilutions  of 
1  :io.      But  as  our  data  are  very  imperfect  and  incomplete  and  little 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


65 


Types 

of 

0 
0 

5j    <V 

t/1  JD 

•0 

Colonies. 

0 

0 
0 

** 

oS 

CO       • 

= 

_ 

tn 

(J) 

£n 

J-     C/3 

d>  a; 

3  -* 

«  'S  -H 

H-2  — 
5  0  c 

t/5 
X 

_fcjO 

IS 

a 

■c 
0 
0 

en 
u 

3 

V 

0 

Brief   Description  of  Stool. 

Source  of 
Specimen. 

U 

z 

Q 

' 

' 

5 

3 

fe 

1 

15 

2 

2 

0 

0 

+ 

+ 

Small  quantity  mucus  supplied 

N.Y.H.D. 

2 

18 

6 

6 

0 

+ 

+ 

,  + 

Greenish-yellow                            N.Y.  H.D. 

3 

18 

0 

0 

0 

0 

+ 

+ 

Greenish  with   trace  of  bloodjN.Y.H  .D. 

4 

18 

0 

0 

0 

0 

+ 

+ 

Yellow  soft  feces 

N.Y.H.D. 

*5 

N.  Y.  D. 

*6 



N.Y.H.D. 

7 

18 

2 

2 

0 

0 

+ 

+ 

Greenish  with  curds;  little  mu- 
cus 

N.Y.H.D. 

8 

16 

0 

0 

0 

? 

+ 

? 

Specimen  in  sterile  bottle 

N.Y.H.D. 

9 

16 

0 

0 

0 

0 

+ 

+ 

Greenish-yellow  curds                1  N.Y. H.D. 

*xo 

MWU      T-> 

11 

18 

8 

8 

0 

0 

+ 

? 

Rec'd  in  sterile  salt  sol. 

N.Y.H.D. 

12 

18 

3 

3 

0 

0 

+ 

? 

Rec'd  in  sterile  salt  sol. 

N.Y.H.D. 

'3 

16 

0 

0 

0 

0 

+ 

+ 

Rec'd  in  sterile  salt  sol. 

N.Y.H.D. 

aH 

21 

0 

0 

0 

+ 

+ 

D 

Dried  mucus;  trace  of  blood 

N.Y.H.D. 

»5 

18 

0 

0 

0 

0 

+ 

+ 

Rec'd  in  salt  sol. 

N.Y.H.D. 

16 

15 

0 

0 

0 

+ 

+ 

+ 

Bloody  mucus  on  rectal  tube 

B.  H. 

'7 

16 

0 

0 

0 

0 

+ 

+ 

Rec'd  in  salt  sol. 

B.  H. 

18 

18 

1 

1 

0 

0 

+ 

? 

Greenish;  much  mucus 

B.  H. 

'9 
^"20 

l6 
16 

7 
0 

7 
0 

0 
0 

0 
0 

+ 
+ 

? 
+ 

Yellow-green;  consid.  mucus 

B.  H. 

21 

Green  ;   semi-fluid 

N.Y.H.D. 

22 

16 

0 

0 

0 

0 

+ 

+ 

Rec'd  in  salt  sol. 

N.Y.H.D. 

23 

•5 

0 

0 

O- 

0 

+ 

+ 

Rec'd  in  salt  sol. 

N.Y.H.D. 

*24 

15 

0 

0 

0 

0 

+ 

+ 

Yellow  curds  rec'd  on  paper 

N.Y.H.D. 

*2; 

B.  H. 
B.  H. 

A     3 
<?26 

9 

4 

4 

0 

0 

+ 

+ 

Green;  little  mucus,  feces 

27 

9 

0 

0 

0 

0 

+ 

+ 

Formed  with  trace  of  mucus; 
much  feces 

B.  H. 

28 

11 

2 

2 

0 

0 

+ 

+ 

Large    green    curds;    consid. 
mucus 

B.  H. 

A29 

*3° 

40 

0 

0 

0 

+ 

+ 

+ 

Large  stool  in  chamber 

N.Y.H.D. 

J5 

2 

2 

0 

+ 

+ 

? 

Small,    foul,    greenish  ;    littlej      B.  H  . 

mucus  and  blood 

ft3' 

20 

5 

5 

0 

+ 

+ 

? 

Small,  with  much  mucus  and       B.  H. 

trace  of  blood 

32 

15 

0 

0 

0 

+ 

+ 

? 

Fluid,  green ;   trace  of  blood. 

B.  H. 

33 

40 

54 

54 

0 

0 

+ 

+ 

Small,  green,    muco-purulent 

B.  H. 

34 

16 

0 

0 

0 

0 

+ 

+ 

Rec'd  in  salt  sol. 

N.Y.H.D. 

35 

21 

0 

0 

0 

0 

+ 

+ 

Green  ;    consid.     mucus   and 
feces 

B.  H. 

*  Cases  5,  6,  10,  25  are  not  included  in  reports  as  illness  of  under-assistant  prevented  them 
from  being  worked  out  completely. 

**  N.Y.H.D.  =New  York  Health  Department;  N.  Y.  D.  —  New  York  Dispensary;  B.  H. 
=  Bellevue  Hospital;  G.  S.  D.=Good  Samaritan  Dispensary. 

a.  Case  14  showed  large  numbers  of  cocci. 

b.  Case  26  at  autopsy  showed  congestion  and  hemorrhages  in  intestine;  cultures  from 
colon  gave  colonies  of  "  Flexner-Harris  "  type  of  B.  dysenteric.  Case  30  at  autopsy  showed 
extensive  ulcerations  of  ileum  and  colon;  mesenteric  glands  enlarged  and  hemorrhagic;  cultures 
from  ileum  and  from  colon  yielded  B.  dysenteriae  (Flexner-Harris),  and  from  mesenteric 
glands  B.  coli  com. ;  Case  31  at  autopsy  showed  ulcerative  colitis  and  ulceration  and  gangrene 
of   appendix. 

c.  Editorial  Note. — In  preparing  this  table  from  the  "Bacteriological  Reports"  No.  20 
was  found  missing  from  the  series. — S.  F. 


66 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


01 

Types  of 

"o 
0 

V 

3 

%% 

3 

in    ■ 

c  .2  — 

Colonies. 

0 
0 

O 
O 

0 
0 

in 

V 

0 

il 

O   3 

n  z 

"S 

X 

E75 

u 

z 

Q 

- 

- 

pq 

§ 

" 

36 

15 

0 

0 

0 

0 

+ 

? 

37 

16 

0 

0 

0 

0 

+   . 

+ 

a3& 

35 

6 

6 

0 

+ 

+ 

+ 

39 

20 

0 

0 

0 

+ 

+ 

+ 

40 

J9 

1 

1 

0 

0 

+ 

+ 

4i 

22 

1 

1 

0 

+ 

+ 

+ 

42 

3° 

0 

0 

0 

0 

+ 

+. 

43 

32 

1 

1 

0 

0 

+ 

+ 

44 

24 

2 

0 

2 

+ 

+ 

0 

45 

20 

8 

0 

8 

0 

+ 

+ 

^46 

24 

0 

0 

0 

+ 

+ 

+ 

<H7 

24 

0 

0 

0 

0 

+ 

-4- 

48 

25 

1 

1 

0 

0 

+    - 

O 

49 

17 

1 

1 

0 

0 

+ 

+ 

^50 

17 

0 

0 

0 

0 

+ 

+ 

*>i 

25 

0 

0 

0 

0 

+ 

+ 

*52 

28 

0 

0 

0 

0 

+ 

+ 

*53 

33 

0 

° 

0 

0 

+ 

+ 

Brief  Description  of  Stool. 


Source  of 
Specimen. 


Watery  brown  on  sterile  pad 

Rec'd  in  sterile  tube 

Bloody  matter  with  feces  on 
rectal  tube 

Dried  specimen 

Green,  large  ;  much  mucus 
and  feces 

Small,  brownish;  mod.  amt. 
mucus;  little  blood 

Greenish    curds 

Feces  and  large  curds;  mod. 
amt.    mucus 

Small  quantity  of  mucus  and 
blood 

Greenish-yellow;  much  mu- 
cus and  feces 

Yellow-green;  much  mucus; 
trace  blood 

Whitish  feces  with  mucus 

Muco-purulent 

Rec'd  in  rectal  tube 

Greenish  curds;  consid.  mu- 
cus 

Greenish-yellow;  much  mucus 

Greenish;  mod.  amt.  mucus, 
feces 

Rec'd  in  rectal  tube 


B.  H. 
N.Y.H.D. 

B.H. 

N.Y.H.D. 
B.H. 

B.  H. 

N.Y.H.D. 
B.  H. 

B.  H. 

G.  S.  D. 

G.  S.  D. 

G.  S.  D. 

B.H. 
G.  S.  D. 

B.  H. 

B.H. 

G.  S.  D. 

G.  S.  D. 


**  N.Y.H.D.  =  New  York  Health  Department;  N.  Y.  D.  =  New  York  Dispensary; 
B.  H.  =  Bellevue  Hospital  ;     G.  S.  D.  =  Good  Samaritan  Dispensary. 

a.  This  case  was  plated  three  times  and  always  contained  an  organism  which  overgrew 
the  plates  in  48  hours.  The  successful  isolation  was  made  by  taking  off  colonies  from  some 
plates  at  the  end  of  24  hours. 

b.  Cases  46,  47,  50,  51,  52,  53  showed  large  numbers  of  cocci. 


can  be  made  out  from  them  of  the  duration  and  severity  of  the  symp- 
toms, we  do  not  regard  them  as  of  sufficient  value  to  include  in  this 
report. 

The  conclusions  which  we  here  draw  from  our  study,  the  main  facts 
and  features  of  which  are  here  presented,  is  that  B.  dysenteriae  can  be 
found  in  all  cases  possibly  of  infantile  diarrhea  in  which  the  discharges 
contain  mucus,  whether  or  not  it  is  accompanied  by  blood.  The  per- 
centage of  cases  in  which  positive  results  occur  will  depend  upon  cer- 
tain conditions  inherent  in  the  material  or  operating  from  without. 
Besides  the  factors  of  freshness  and  cleanliness  in  the  stools  and  the 
reaction  of  the  culture  medium  used  for  plating  which  are  to  be  re- 
garded, we  have  found,  as  unfavorable,  watery  condition,  much  feces 
and  large  number  of  cocci  in  the  discharges. 


REPORT  OF  LOUISE  CORDES,  M.D., 
Pathologist  to  the  New  York  Infirmary   for  Women  and  Children. 

During  the  summer  months  stools  from  51  cases  of  gastro-intestinal 
disturbance  in  infants  and  children  were  examined  in  the  Laboratory 
of  the  New  York  Infirmary  for  Women  and  Children,  for  the  presence 
of  Bacillus  dysenteriae. 

Material  was  obtained  from  cases  treated  at  the  Nursery  and  Child's 
Hospital  and  the  New  York  Infirmary  for  Women  and  Children ;  one 
case  was  seen  in  the  Babies'  Hospital  dispensary. 

The  Infirmary  series  included  dispensary  and  outpractice  as  well  as 
hospital  cases. 

Stools  from  10  cases  were  obtained  from  the  Nursery  and  Child's 
Hospital,  9  from  the  New  York  Infirmary  and  31  from  the  dispensary 
and  out-patient  department  of  the  Infirmary. 

The  stools  were  not  selected,  material  from  all  cases  of  gastro-intesti- 
nal disorder,  even  those  showing  the  mildest  symptoms,  having  been 
examined. 

The  material  was  in  a  great  many  cases  obtained  fresh  and  plated 
at  once ;  in  some  of  the  outdoor  cases  stools  were  brought  from  one  to 
two  hours  after  being  passed,  but  not  later.  The  Bacillus  dysenteriae 
was  found  in  the  stools  of  26  cases — or  in  51  per  cent.  Two  cases  of  5 
and  10  years  respectively  are  included  in  the  list,  the  remainder  being 
under  2)^  years  old. 

The  ages  of  the  children  whose  stools  were  found  to  contain  the 
Bacillus  dysenteriae  ranged  as  follows  : 

Under  6  months 4 

From  6-12  months 5 

From  12-18  months 5 

From  18  months  to  2^4  years 10 

Over  5  years 2 

In  the  cases  giving  positive  results,  the  character  of  the  stools  was 
as  follows  :  Soft  greenish-yellow  feces  with  much  mucus  and  no  blood 
(in  one  of  these  cases  there  was  a  history  of  blood),  14;  green  feces 
with  little  or  a  moderate  amount  of  mucus  and  no  blood,  6 ;  green  or 


68  Louise  Cordes. 

yellow  feces  without  mucus  or  blood,  2 ;  brownish-yellow  liquid  without 
mucus  or  blood  (in  this  case  there  had  been  a  previous  attack  during 
which  the  stools  were  not  watery,  but  consisted  of  green  and  yellow 
feces  and  mucus),  1 ;  green  feces,  mucus  and  blood  (two  of  the  stools 
in  this  series  contained  curds  and  one,  undigested  food),  3. 

The  negative  stools  showed  the  following  characters:  Green  feces 
with  much  mucus  and  no  blood,  1 ;  green  or  yellow  feces  with  a  moder- 
ate amount  of  mucus  and  no  blood,  6 ;  green  or  green  and  yellow  feces 
with  little  mucus  and  no  blood,  6 ;  green  or  green  and  yellow  feces  with 
much  or  a  moderate  amount  of  mucus  and  blood,  5 ;  greyish-green  and 
yellow,  or  green  feces  no  mucus,  no  blood  (two  of  these  stools  con- 
tained undigested  food  and  one,  curds),  7. 

The  frequency  of  the  stools  in  the  cases  in  which  Bacillus  dysenteric 
was  found  varied  considerably;  there  were,  in  24  hours, 
4-6     stools   in   6  cases 


5-IO 

a 

'    6     " 

6-12 

a 

"    1      " 

7 

it 

'    2     " 

10-12 

"    8      " 

12-15 

" 

"    1      " 

15-20 

. 

"    2      " 

In  the  negative  cases  the  free 

uenc> 

of  the  stoc 

12-20 

in   1 

case 

10  or 

10-12 

in  4  cases 

6-8 

in  2 

cases 

5-7 

"  4 

" 

3-5 

"  8 

a 

2-5 

"  3 

u 

2-3 

"  3 

ii 

In  25  stools  the  acid  type  of  Bacillus  dysenteriae  was  found ;  the 
alkaline  type  was  isolated  from  one  case. 

Agglutination  with  the  anti-dysenteric  horse  serum  (Harris)  was 
positive  in  dilutions  of  1-3000  or  1-3500  with  the  bacillus  of  the  "Flex- 
ner-Harris"  type  obtained  from  6,  in  a  dilution  of  1-2000  in  12,  in 
1-1000  in  7  cases.  These  organisms  showed  agglutination  with  the 
"Shiga"  anti-dysenteric  serum  in  dilutions  of  1-200  or  1-500  and  in 
1  case  in  1-1000. 

The  bacillus  of  the  alkaline  (Shiga)  type  isolated  from  one  case  gave 
a  positive  reaction  with  the  "Shiga"  anti-dysenteric  serum  in  a  dilution 
of  1-7500  and  with  the  "Harris"  serum  in  1-2000. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


69 


<u 

-a 

D 

c 

otal    No.    of 
Colon  i  e  s 
Transplanted. 

Number    of 
Colonies    of 
B.  Dysenteric 

Type  of 

Bacilli. 

0 

c 

a  . 

"O 

; 
0 

11 
n    55 

S     C 

0     1) 

2    <u 

Description  of  Stool. 

Agglutination. 

u 

c 

6 

c/5 

X 

•75 

0 

6 
> 

O'C 

0 

2 

Z 

12 

'-, 

- 

- 

5  : 
0 

f  + 

CL, 

"Z 

w 

60 

3 

3 

0 

Solid  green  and  yellow 

B.H.D. 

1 

mod.  mucus 

2 

8 

— 

4 

4 

0 

+ 

f  + 

Semi-solid  green    curds 
much  mucus 

i:.50 

N.C.H. 

3 

16 

— 

0 

— 

— 

+ 

t-  + 

Semi-solid  green  ;   mod. 
mucus, very  little  blooc 

1:50 

N.C.H. 

4 

12 

— 

0 

— 

— 

0 

f  + 

Pasty,  brownish-yellow 

1:50 

N.C.H. 

5 

4 

— 

0 

— 

— 

0 

f  + 

Yellow;  pasty  with  mod. 
mucus 

1:50 

N.C.H. 

6 

8 

— 

0 

— 

— 

+ 

t-  + 

Green-y  e  1 1  0  w  ,      semi- 
solid ;  little  blood 

1:50 

N.C.H. 

7 

4 

— 

0 

— 

— 

0  - 

t-  + 

Green,  semi-solid;   little 
mucus 

N.C.H. 

8 

8 

— 

0 

— 

— 

0  - 

1-  + 

Green,  semi-solid;  mod. 
mucus 

1:50 

N.C.H. 

9 

12 

50 

4 

4 

— 

+  - 

h  + 

Soft,  yellow  ;  much  mu- 
cus, little  blood 

1:50 

N.C.H. 

10 

12 

— 

— 

— 

— 

+  - 

h  + 

Soft,   green  and  yellow; 
little  blood 

1:50 

N.C.H. 

11 

12 

— 

0 

— 

— 

0    c 

>  + 

Soft  feces 

1:50 

N.C.H. 

12 

12 

— 

0 

— 

— 

0    - 

-  + 

Pasty,  green;  mod.   mu- 
cus 

1:50 

N.Y.I. 

13 

8 

— 

0 

— 

— 

0    c 

)  + 

Semi-solid 

1:50 

M.Y.I. 

14 

8 

— 

0 

— 

— 

0    H 

-  + 

Semi-solid  ;     very    little 
mucus 

1:50 

N.Y.I. 

15 

16 

75 

8 

8 

0 

0    H 

-  + 

Green  and  yellow,  semi- 
solid; much  mucus 

1:50 

N.Y.I. 

16 

[2 

82 

2 

2 

0 

0    H 

-  + 

Green,    yellow;    little 
mucus 

1:  50 

N.Y.I. 

17 

16 

— 

0 

— 

— 

0    c 

+ 

Semi-liquid,    green    and 
yellow 

1:53 

N.Y.I. 

18 

12 

25 

1 

1 

0 

0    c 

+ 

Soft,  yellow  green 

1:50 

N.Y.I. 

19 

8 

0 

— 

— 

0    4 

-  + 

Soft,    green;    very   little 
mucus 

1:50 

N.Y.I. 

20 

12 

— 

0 

— 

— 

0    4 

-  + 

Soft,  green  and   yellow; 
trace  of  mucus 

1:50 

N.Y.I. 

21 

8 

26 

8 

8 

0 

0    4 

-  + 

Soft,     yellow  ;      consid. 
mucus 

1:50 

16 

65 

S 

5 

0 

O    -i 

-  + 

Soft,    yellow ;    consid. 

N.Y.I. 

1*2 

mucus 

23 

12 

— 

0 

— 

— 

O    C 

+ 

Soft,  green  and  yellow 

1:50 

N.Y.I. 

24 

8 

— 

0 

— 

— 

O    -f 

+ 

Soft,  green;  mod.  mucus 

1:50 

N.Y.I. 

25 

8 

32 

3 

3 

0 

O    -f 

+ 

Soft,  yellow,  green ;   lit- 
tle mucus 

1:50 

N.Y.I. 

26 

8 

— 

0 

— 

— 

0    c 

+ 

Soft,  green  and  yellow 

1:50 

N.Y.I. 

27 

8 

— 

0 

— 

— 

0  -t 

+ 

Semi-solid,     green     and 
yellow;  mod.  mucus 

1:50 

N.Y.I. 

28 

8 

65 

6 

6 

0 

0  -f 

+ 

Soft   green,   consid.  mu- 
cus 

1:50 

N.Y.I. 

29 

8 

28 

1 

1 

0 

O     ■+ 

+ 

Soft,  green  and    yellow; 
little  mucus 

1:50 

M.Y.I. 

8 

J37 

2 

2 

0 

O     ■+ 

+ 

Soft,  green,  yellow;  con- 

N.Y.I. 

3° 

sid.  mucus 

8 

61 

3 

3 

0 

O    -t- 

+ 

Soft,  green    curds;    con- 

N.Y.I. 

31 

sid.  mucus 

32 

8 

— 

0 

— 

— 

O    + 

+ 

Soft,  green;  little  mucus 

1:50 

N.Y.I. 

B.H.D.. 
:New  York 


=  Babies'  Hospital   Dispensary.     N.C.H.=  Nursery  and  Child's  Hospital.     N.Y.I. 
Infirmary. 


7o 


Louise  Cordes. 


— 

c 
2 

0  w  aj 
Z  0  5T 

-=  0  R 

Number      of 
Colonies    of 
B.  Dysenteric. 

Type  of 

Bacilli. 

c 

7. 

- 

-0 

0 

c 

0 
0 

7. 

c 

CA 
O 

a 

"3 

: 

•s\ 

■s. 

V 

- 

Description  of  Stool. 

Agglutination. 

ns 
U 

"o 

d 

in 

en 

O 
Hi 

aj 
> 

U 

z 

41   ej 

O 
X 

33 
34 

16 
8 

150 
27 

3 

5 

3 

5 

0 
0 

0 

0 

0 

? 
+ 

Vellow  and  watery    (bit 

of  gauze  plated) 
Soft,  green,  yellow;  con- 

sid.  mucus 

1:50 
1:50 

N.Y.  I. 

X.Y.I. 

35 

12 

22 

2 

0 

2 

0 

+ 

+■ 

Soft,  yellow,  brown;  lit- 
tle mucus 

1:50 

N.Y.I. 

36 

8 

130 

3 

3 

0 

0 

+ 

+ 

Semi-solid;   little  mucus 

1:50 

N.Y.I. 

37 

8 

I4O 

4 

4 

0 

~ 

+ 

+ 

Soft,  yellow;   much  mu- 
cus, trace  of  blood 

1:50 

N.Y.I. 

38 

8 



0 

— 

— 

0 

+ 

+ 

Soft,  yellow;  undigested 
food;  very  little  mucus 

1 :  40 

N.Y.I. 

39 

12 

41 

1 

1 

0 

+ 

+ 

- 

Soft,  green;  consid.  mu- 
cus 

1:50 

N.Y.I. 

40 

8 

166 

5 

5 

0 

0 

+ 

+ 

Semi-solid,  green  ;    con- 
sid. mucus 

1:50 

N.Y.I. 

41 

12 

15 

2 

2 

0 

0 

+ 

+ 

Soft,  yellow;  undigested 
food,  consid.  mucus 

1 :  40 

N.Y.I. 

42 

16 

— 

0 

— 

— 

0 

+ 

+ 

Soft,  green ;  much  mucus 

1 :  40 

N.Y.I. 

43 

44 

12 

T2 

- 

0 
0 

— 

— 

0 
0 

+ 
0 

+ 

Soft,  green  ;  much  mucus 
Semi-solid,  greenish-yel- 
low 

1:50 
1 :  40 

N.Y.I. 

N.Y.I. 

45 

12 

75 

2 

2 

0 

- 

- 

+ 

Soft,    greenish  ;      much 
mucus,  little  blood 

1 :  40 

N.Y.I. 

46 

8 

— 

4 

4 

0 

0 

+ 

+ 

Soft, yellow;  undig.  food, 
much  mucus 

1:50 

N.Y.I. 

47 

8 

47 

6 

6 

0 

~ 

T 

- 

Soft,  green  and  yellow; 
much  mucus 

1 :  40 

N.Y.I. 

48 

12 

— 

0 

— 

— 

0 

+ 

- 

Semi-fluid,  green ;    mod. 
mucus 

1:50 

N.Y.I. 

49 

12 

— 

0 

— 

— 

0 

O 

- 

Soft,  green,  yellow 

1:50 

N.Y.I. 

50 

8 

58 

3 

3 

— 

0 

+ 

- 

Semi-fluid,  brown;  mod. 
mucus 

1:50 

N.Y.I. 

5i 

12 

90 

14 

14 

0 

+ 

Semi-solid,    green,    yel 
low;  much  mucus 

1:50 

N.Y.I. 

B.H.D.  =  Babies'  Hospital    Dispensary.     N.C.H.  =  Nursery  and  Child's  Hospital.      N.Y.I. 
=  New  York  Infirmary. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


7i 


The  blood  of  46  cases,  22  of  which  yielded  the  Bacillus  dysenteriae 
was  tested  with  the  "Flexner-Harris"  and  "Shiga"  types  of  the  dysen- 
tery bacillus  in  a  dilution  of  1-50.  Of  the  22  cases  in  which  the  bacillus 
was  observed,  10  gave  a  positive  reaction  on  the  4th  to  the  24th  day 
of  the  disease;  12  failed  to  give  a  reaction,  11  of  these  having  been 
tested  on  the  2nd  to  the  8th  day  of  the  disease  and  1  on  the  twelfth 
day.    A  reaction  was  obtained  in  3  negative  cases. 

The  blood  in  the  22  negative  cases,  in  which  no  reaction  was  ob- 
tained, was  examined  as  follows : 

2nd  day  of  the  disease    3  cases 


3rd 

'      " 

7th    ' 

t         a 

8th     ' 

.          a 

9th     ' 

i         11 

10th     ' 

(          a 

nth     ' 

i          u 

14th     ' 

i         tt 

15th     ' 

i          a 

1 8th     ' 

i          a 

25th     ' 

i          11 

3rd  week  " 

6th     " 

2d  mc 

nth  " 

In  those  cases  in  which  the  stools  were  plated,  more  than  one  hour 
after  they  were  passed,  the  following  results  are  shown : 

(  Positive     2 
\y2  hours  after 3  1  m       *■ 

7  )  Negative  1 

2     hours  after 8    All  negative 

The  table  expresses  in  brief  form  the  main  facts  of  my  study. 


REPORT  OF  W.  W.  WAITE,  Stud. Med. 

My  report  is  based  upon  the  bacteriological  examination  of  47  cases 
of  diarrhea  in  children.  The  examinations  were  conducted  in  the 
Pathological  Laboratory  of  the  Johns  Hopkins  University.  The  speci- 
mens were  drawn  chiefly  from  the  dispensary  of  the  Johns  Hop- 
kins Hospital.  Of  the  47  cases  studied  40  were  supplied  from  the  dis- 
pensary and  7  from  the  private  practice  of  physicians  in  Baltimore. 
For  the  latter  I  wish  to  thank  Drs.  Booker  and  Thayer;  and  for  the 
former,  Dr.  Amberg. 

The  report  is  based  chiefly  upon  the  results  of  my  own  examinations 
but  as  I  had,  during  a  short  period,  the  valuable  help  of  Mr.  Shorer, 
who  was  detached  from  New  York  in  order  to  bring  me  assistance,  I 
wish  to  acknowledge  the  great  aid  that  he  rendered  me.  He  brought 
into  the  work  the  advantage  of  improvements  in  method  of  isolating 
the  bacillus  with  which  the  richer  results  of  the  investigation  in  New 
York  and  elsewhere  had  been  achieved.  Although  he  studied  a  very 
small  number  of  cases  during  his  stay  in  Baltimore  his  results  are 
striking  and  noteworthy  and  have  been  indicated  in  the  accompanying 
table. 

I  am  confident  that  at  the  beginning  of  the  summer  I  made  the  seri- 
ous mistake  of  attempting  to  study  too  large  a  number  of  cases ;  and 
as  the  facilities  for  carrying  on  the  study  under  the  most  favorable  con- 
ditions had  not  then  been  completed,  my  results  are  less  complete  than 
I  wish.  But  I  am  giving  the  records  as  I  have  them  and  shall  comment 
no  further  upon  the  number  of  failures  to  secure  the  bacillus  of  dysen- 
tery which  they  indicate.  It  remains,  however,  for  me  to  add  that  from 
two  cases  in  which  I  failed  to  find  the  bacillus  this  organism  was 
afterwards  isolated  by  Dr.  Bassett  at  the  Wilson  Sanitarium  to  which 
institution  the  children  were  taken  for  treatment. 

Of  the  47  cases  studied  bacteriologically  19  yielded  the  bacillus  of 
dysentery,  or,  stated  in  percentages,  in  40  per  cent,  of  the  cases  that 
organism  was  isolated  in  cultures.  The  type  of  bacillus  found  was 
chiefly  the  "Flexner-Harris"  organism,  although  in  two  instances  the 
"Shiga"  type  was  obtained.  In  no  instance  was  a  mixture  of  the  two 
types  met  with. 

For  the  most  part  the  number  of  colonies  of  dysentery  bacilli  isolated 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  73 

was  small,  although  in  a  few  instances  the  number  was  strikingly 
large.  Thus  in  cases  44  and  46,  30  to  50  per  cent,  of  the  transplanted 
colonies  proved  to  be  that  organism.  The  table  states  in  the  positive 
cases  the  number  of  colonies  transplanted  from  the  plates  and  the  num- 
ber of  tubes  of  the  dysentery  bacillus  which  were  secured  from  them. 

The  methods  which  I  pursued  in  this  study  were,  until  Mr.  Shorer's 
visit,  those  laid  down  by  Vedder  and  Duval ;  and  the  identification  of 
the  bacilli  as  those  of  dysentery  was  made  by  the  tests  now  usually 
employed.  The  absence  of  gas-formation  in  sugar  media,  the  lit- 
mus-milk reaction,  the  appearances  of  the  colonies,  etc.,  upon  the 
ordinary  culture  media  and  finally  the  agglutination  reactions  with 
anti-dysenteric  horses'  serum  were  all  observed  and  noted.  For  the 
differentiation  of  the  two  types  of  bacilli  the  litmus-mannite-agar-agar 
of  Lentz  was  used.  After  Mr.  Shorer  had  introduced  me  to  the  use 
of  Hiss'  semi-solid  jelly  for  the  more  ready  separation  of  colonies  of 
B.  coli  communis  and  some  other  bacilli  from  those  of  the  dysentery 
bacillus  I  continued  to  employ  in  my  later  work  that  method  of  isolating 
the  last  named  organism  from  the  plates. 

A  scrutiny  of  the  table  will  show  that  in  my  work  I  had  the  ad- 
vantage of  securing  material  for  plating  in  a  fresh  condition,  as  the 
specimens  were  taken  for  me  at  the  dispensary  in  rectal  tubes.  On 
the  other  hand,  this  method  of  securing  specimens  for  bacteriological 
examination  often  precluded  the  study  of  the  contents  of  the  higher 
bowel,  which  fact  should  be  considered  in  interpreting  my  results.  In 
this  connection  it  is  proper  to  draw  attention  to  the  uniformly  suc- 
cessful efforts  in  obtaining  the  bacillus  of  dysentery  from  cases  in 
private  practice  where  natural  discharges  were  used  for  the  plating. 

The  manner  of  securing  the  specimens  was  such  as  to  make  the 
question  of  the  presence  or  absence  of  blood  in  the  natural  discharges 
very  difficult  to  answer.  The  histories  given  by  mothers  in  dispensary 
practice  are  very  unreliable  upon  such  points  and,  unfortunately,  even 
the  most  careful  insertion  of  the  rectal  tube  will  often  be  followed  by  a 
slight  abrasion  of  the  mucous  membrane  which  leads  to  small  bleedings. 
We  have  tried  to  eliminate  this  factor  in  our  descriptions  of  the  speci- 
mens examined,  but  with  doubtful  success.  On  the  other  hand,  mucus  is 
readily  obtained  by  the  tube  method  and  cannot  be  held  to  bear  any 
close  relationship  with  the  amount  of  mucus  which  might  be  present 
in  these  pathological  cases  in  the  natural  discharges.  As  one  glances 
over  the  table  he  is  struck  with  the  almost  constant  presence  of  mucus 
and  feces  in  the  specimens  examined  and  the  far  less  frequent  presence 
of  blood.     For  example,  feces  are  encountered  in  all  cases  but  one, 


74 


W.  IV.  Waite. 


1) 

T3 

s 

d 

2 

W  -r-J 

.Si  4> 
O  g 

2 

No.  of  Colonies 
of  B.   Dysen- 
teric. 

IO 

47 

4 

ID 

— 

0 

12 

— 

0 

IO 

— 

0 

IO 

45 

5 

IO 

— 

0 

IO 

— 

0 

18 

— 

0 

8 

— 

0 

8 

— 

0 

IO 

— 

0 

IO 

20 

1 

12 



0 

18 

79 

3 

12 

— 

0 

9 

— 

0 

IO 

— 

0 

15 

172 

3 

IO 

— 

0 

IO 

— 

0 

IO 

17 

1 

IO 

— 

0 

IO 

— 

0 

18 

57 

5 

16 

43 

2 

!9 

25 

3 

20 

76 

4 

16 

- 

0 

18 

— 

0 

20 

— 

0 

12 

- 

0 

14 

- 

0 

18 

— 

0 

18 

- 

0 

23 

- 

0 

16 

- 

0 

18 

— 

0 

i8 

— 

0 

37 

— 

0 

Type  of 
Bacilli. 


0 

0 

7. 

a 

P 

3 

a 

c 

0 

■r. 

a 

yj 

■V 

*j 

V 

+ 

+ 

+ 

+ 

+ 

+ 

? 

+ 

+ 

+ 

0 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

- 

+ 

+ 

+ 

+ 

+ 

0 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

0 

+ 

0 

+ 

+ 

+ 

+ 

? 

+ 

+ 

+ 

+ 

+ 

+ 

0 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

+ 

Description  of  Material  Used. 


Notes. 


Obtained  by  tubing;;    thin  and  gray 
Obtained  by  tubing-;  thin  and  clear 
Obtained  by  tubing-;  dark  and  green 
Obtained    by   tubing  ;    dark,     reddish- 
brown 
Obtained  by  tubing;  thin,  greenish-yel- 
low 
Obtained  by  tubing;    thin  and  yellow 
Obtained  by  tubing;   mucus 
Obtained  by  tubing;    dark  brown,  fecal 

and  mucus 
Obtained  by  tubing;    pale  mucus 
Obtained  by  tubing;  thin  and  brown 
Obtained  by  tubing;  thin  and  clear 
Obtained  by  tubing;   yellow  mucus 
Obtained  by  tubing;   thin,  greenish-yel- 
low 
Obtained  on    napkin;    pasty,    brownish 

yellow 
Obtained  by  tube;  thin,  greenish  mucus 
Obtained    by  tube;     mucus    and    little 

blood 
Obtained  by  tube;  small  and  pus-like 
Obtained  by  tube;   yellow,  green  slime 
Obtained  by  tube;  yellow,  green  slime 
Obtained  by  tube;   blood-stained  mucus 
Obtained   by    tube;    thin,    mucus    and 

blood 
Obtained  by  tube;   thin  mucus 
Obtained  by  tube;   thin,  yellow  feces 
Obtained  by  tube;  green,  muco-fecal 
Obtained  by  tube;  mucus 
Obtained  by  tube  ;    bloody  mucus  and 

feces 
Obtained  by   tube  ;    green    mucus  and 

feces 
Obtained  by  tube;   gray,  with  little  mu- 
cus 
Obtained  by  tube;   thin,  yellow  feces 
Obtained  by  tube;  feces  with  little  mu- 
cus 
Obtained  by  tube;  feces  with  little  mu- 
cus 
Obtained  by  tube;  feces  with  green  mu- 
cus 
Obtained  by  tube;  green  feces  and  curds 

with  mucus 
Obtained  by  tube;  green  feces  with  mu- 
cus 
Obtained  on  pad;  yellow  feces,  little  mu- 
cus 
Obtained  by   tube;  thick,  yellow  feces, 

little   mucus 
Obtained  by   tube  ;    thin,    yellow    feces 

and   mucus 
Obtained  by  tube;  thick,  green  feces,  lit- 
tle mucus 
Obtained  by  tube;  green  feces  with  mu- 
cus 


r  A 


A,  examined  by  W.  W.  W. 
C,  examined  by  E.  H.  Shorer. 


B,  reported   positive   by    Dr.   Bassett,   Wilson  Sanitarium. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


75 


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Z 

40 

3^ 

— 

0 

41 

18 

70 

2 

42 

16 

60 

5 

43 

18 

87 

1 

44 

18 

38 

16 

45 

10 

22 

3 

4~> 

1S 

48 

13 

47 

24 

325 

1 

Type  of 
Bacilli. 


16 


3 

13 


Description  of  Material  Used. 


Obtained  by  tube;  green,  thin  feces  with 

mucus 
Obtained    on    napkin;       partly    dried, 

blood-flecked  stool 
Obtained  by  tube;    small  amt.  feces  and 

mucus 
Obtained  by  tube;  green  mucus 
Obtained  on  napkin ;   green   feces  with 

mucus  and  blood  flecks 
Obtained  on  napkin  ;  thick  mucus 
Obtained  on  napkin;   green  mucus 
Obtained  on  napkin;   yellow  feces  with 

mucus  and  blood 


Notes. 


A,  examined   by   W.  W.  W. 


mucus  in  all  cases  but  four,  and  blood  was  absent  in  30  instances — 
hence  in  two-thirds  of  the  cases  studied. 

If  we  consider  only  the  instances  (16  analyzed)  in  which  the  dysen- 
tery bacillus  was  found  we  find  that  blood  occurred  8  times  and  mucus 
and  feces  in  all.  Of  the  3  cases  not  included  in  the  analysis  in  one  the 
specimen  was  dried  (case  4)  and  in  two  the  bacillus  was  isolated  later 
by  Dr.  Bassett  at  the  Wilson  Sanitarium. 


REPORT  OF  ARTHUR  I.  KENDALL, 

Boston. 

From  June  15th  to  September  15th,  1903,  I  was  engaged  under 
the  auspices  of  the  Rockefeller  Institute  for  Medical  Research  in  the 
investigation  of  the  bacteriology  of  cases  of  diarrhea  in  children  with 
especial  reference  to  the  occurrence  of  the  bacillus  of  dysentery  in  the 
excreta.  The  children  from  whom  I  obtained  specimens  for  examina- 
tion were  being  cared  for  at  the  Boston  Floating  Hospital,  although 
in  this  report  there  will  be  included  three  cases  of  infantile  diarrhea 
which  were  investigated  at  the  Infant's  Hospital. 

Before  I  take  up  the  subject  matter  of  this  report  I  wish  to  express 
my  great  indebtedness  for  assistance  and  many  courtesies  to  the  fol- 
lowing gentlemen  without  whose  cordial  cooperation  this  study  would 
have  been  impossible :  The  Managers  and  Board  of  Directors,  Drs. 
Hastings,  Fennessey,  Sturgis  and  Shay  of  the  medical  staff,  Drs.  Fair- 
banks and  Breck  of  the  visiting  staff  of  the  Boston  Floating  Hospital, 
Drs.  Durgin  and  Hill  of  the  Board  of  Health,  who  generously  put  at 
my  use  the  facilities  of  the  Bacteriological  Laboratory  of  the  Board,  and 
Mr.  Paul  Lewis  for  his  valuable  aid  in  the  latter  part  of  the 
investigation. 

In  the  course  of  the  summer,  stools  from  35  children  were  studied — 
of  these  35  cases  of  intestinal  disturbance,  4  were  due  to  causes  which 
exclude  them  from  consideration  as  a  part  of  the  study :  thus  two  were 
cases  of  tuberculosis,  one  a  case  of  typhoid  fever  and  one  of  proctitis  of 
transient  character.  Although  they  will  not  be  considered  further  in 
this  report  they  are  of  interest  as  examples  of  intestinal  disease  in  which 
even  very  careful  and  often  prolonged  search  failed  to  disclose  the  pres- 
ence of  the  bacillus  of  dysentery. 

The  exclusion  of  these  four  extraneous  examples  of  diarrheal  dis- 
ease reduces  the  number  of  cases  investigated  to  31,  of  which  number 
29  were  found  to  yield  cultures  of  Bacillus  dysenteriae — a  positive  re- 
sult in  93.5  per  cent.  With  this  introduction  I  will  pass  to  a  de- 
scription of  my  methods  and  the  details  of  the  results  yielded  by  them. 

Culture  Media. — For  the  plates  I  employed  plain  agar-agar  made 
by  Hill's  method  (Committee  of  the  American  Public  Health  Associa- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  77 

tion)  in  which  the  reaction  was  +5  instead  of  +15  as  recommended 
by  the  committee.  The  reason  for  the  change  was  the  more  luxuriant 
growth  of  the  bacillus  of  dysentery  upon  a  medium  of  that  reaction. 
Indeed  upon  it  the  colonies  of  the  dysentery  bacillus  grew  often  to  a 
size  of  2-3  mm.  in  24  hours. 

For  the  differentiation  of  the  types  of  the  bacillus,  mannite-litmus- 
agar  made  also  by  Hill's  method  and  containing  1  per  cent  agar-agar 
and  deeply  tinted  with  litmus  was  used.  For  the  separation  of  the 
gas-producing  from  non-gas-producing  colonies  in  the  original  trans- 
plantations I  used  throughout  the  greater  part  of  the  summer,  glucose- 
agar,  also  prepared  by  Hill's  method,  but  later,  after  Mr.  Lewis' 
arrival  and  at  his  suggestion,  I  employed  the  semi-solid  jelly  of  Hiss 
in  which  more  rapid  and  certain  gas-formation  was  detectable. 

The  other  media  including  litmus-milk  were  prepared  in  the  ordi- 
nary manner;  the  litmus-milk  was  sterilized  by  the  discontinuous  or 
fractional  method  in  an  Arnold's  sterilizer. 

Since  the  plates  were  poured  at  the  Hospital  and  studied  at  the 
laboratory,  which  were  separated  by  a  considerable  distance,  the  steril- 
ized Petri  dishes  were  carried  in  sterile  copper  boxes  from  and  to  the 
laboratory.    In  this  way  ordinary  contaminations  were  entirely  avoided. 

Bacteriological  Methods. — The  plating  of  the  specimens  of  dejecta 
was  done  immediately  or  quickly  after  the  passage.  At  first,  rather 
heavy  suspensions  were  made  and  from  them  a  second  more  dilute  sus- 
pension was  prepared  by  transferring  6  loops  of  the  former  to  a  second 
tube  of  bouillon.  The  plates  were  inoculated  from  this  second  mix- 
ture using  2-4-6-8  loops  for  the  several  tubes  of  agar-agar.  As  a 
rule  eight  plates  were  made  from  a  single  specimen  this  number  being 
necessitated  by  the  difficulty  of  transportation  of  the  sterile  dishes  from 
the  laboratory  to  the  boat  and  back  again  to  the  laboratory.  Later, 
one  loop  of  the  material  was  transferred  to  a  tube  of  sterile  water  and 
this  weak  suspension  then  employed  in  seeding  the  plates.  This  latter 
method  gave  more  uniform  and  satisfactory  results. 

After  a  given  case  was  started,  samples  of  the  dejecta  were  plated 
at  intervals  of  not  more  than  four  days,  until  the  bacillus  of  dysentery 
was  obtained  in  culture  or  had  finally  eluded  detection  in  the  rather 
large  number  of  colonies  among  which  it  had  been  looked  for.  In 
my  hands  this  procedure  was  more  satisfactory  than  the  alternative 
one  of  securing  a  larger  number  of  plates  from  one  sample  of  the  dis- 
charges from  the  bowel.  The  plates  were  incubated  at  370  C.  in  a 
moist  incubator  which  I  found  to  possess  advantages  over  the  dry 
oven. 


78  Arthur  I.  Kendall. 

Transplantation  of  colonies  was  begun  after  18  hours  of  incuba- 
tion. In  about  one-half  of  the  plates  the  surface  colonies  remaining 
were  now  marked  with  the  wax  pencil  and  additional  colonies  of  the 
"Shiga  bacillus"  appearance  were  removed  in  the  same  way  at  intervals 
of  24  hours  until  success  attended  the  search.  The  bacillus  of  dysentery 
was,  as  a  rule,  recovered  among  the  colonies  transplanted  at  the  first 
24-hour  period.  In  a  few  instances,  however,  it  was  obtained  from 
the  marked  plates  and  not  from  the  unmarked  and  hence  at  a  later 
period.  I  am  of  the  opinion  that  the  early  recovery  of  the  bacillus  at 
the  end  of  24  hours  of  incubation  of  the  plates  arose  from  the  favorable 
character  of  the  agar-agar  medium  as  prepared  by  the  Hill  method 
since  the  growth  upon  it  is  strikingly  luxuriant'. 

The  final  identification  of  the  organisms  supposed  to  be  B.  dysen- 
terise  was  completed  by  means  of  a  study  of  the  morphology,  the 
cultural  characters  upon  the  usual  media,  and  the  behavior  towards 
anti-dysenteric  horses'  serum  supplied  by  Dr.  Flexner.  The  separation 
of  the  types  now  recognized — the  "Flexner-Harris"  and  "Shiga" — was 
effected  through  the  use  of  the  litmus-mannite-agar. 

The  biological  characters  and  cultural  properties  of  the  types  of  the 
bacillus  of  dysentery  just  mentioned  are  so  well  known  or  can  be  seen 
so  readily  in  the  publications  of  Yedder  and  Duval,  Duval  and  Bas- 
sett  and  Gay  and  Duval,  that  they  will  not  be  described  here.  But 
I  wish  to  draw  attention  to  certain  bacilli  having;  certain  close  re- 
semblances to  B.  dysenteriae,  but  which  differ  from  that  organism  in 
their  ultimate  action  upon  the  litmus-milk  medium.  What  relationship, 
if  any  exists,  is  borne  by  these  bacilli  to  the  dysentery  bacillus  I  am  not 
able  to  state. 

The  typical  dysentery  bacilli  cause  no  coagulation  of  milk,  and  at 
first  produce  a  weak  acidity,  which  reaction  is  brought  back  to  ampho- 
teric in  about  72  hours,  after  which  a  mild  and  permanent  alkalinity 
makes  its  appearance.  I  encountered  two  "varieties"  of  bacilli  acting 
upon  litmus-milk  in  the  following  manner : 

a.  The  reaction  becomes  at  first  acid,  then  alkaline  and  finally  and 
permanently,  after  about  two  weeks,  acid. 

b.  The  reaction  becomes  at  first  acid,  then  amphoteric  and  finally 
and  permanently  but  slowly  decidedly  alkaline. 

These  ''varieties"  of  bacilli  agglutinate  with  the  anti-dysenteric 
serum  of  the  horse ;  they  are,  however,  not  included  in  the  table  as 
"dysentery  bacilli."  They  were  often  associated  in  the  intestinal  con- 
tents with  the  typical  organisms. 

In  two  instances  I  met  with  what  at  first  appeared  to  be  a  para- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  79 

doxical  result  in  the  cultures.  Organisms  were  obtained  from  the 
plates,  which  gave  all  the  reactions  of  B.  dysenteriae,  but  upon  subse- 
quent investigation,  some  5  weeks  later,  gas  production  in  glucose 
media  was  found  to  be  produced  by  them.  The  explanation  of  this 
anomalous  behavior  of  the  dysentery  bacilli  was  ascertained  by  plating 
the  suspicious  cultures,  when  a  small  number  of  colon  bacilli  were  dis- 
covered to  be  mingled  with  the  former  organisms.  I  mention  this 
experience  in  order  to  point  the  moral  that,  in  attempting  isolation  of 
intestinal  bacteria  directly  from  the  discharges,  colony  appearance  is 
not  necessarily  the  equivalent  of  purity,  and  hence  equivocal  and  con- 
fusing results  of  subcultures  may  easily  be  the  result  of  admixtures 
and  not  necessarily  due  to  "variations"  in  the  prevailing  form  of  micro- 
organism. 

Concerning  the  number  of  dysentery  bacilli  in  the  discharges,  my 
experience  does  not  permit  me  to  hazard  a  statement.  If  the  number 
of  bacilli  recoverable  from  the  plates  be  taken  as  an  index  of  relative 
proportion,  then  they  must  be  regarded  as  in  the  great  minority  as 
compared  with  the  other  intestinal  bacteria  which  grow  upon  the  plates. 
When,  however,  we  stop  to  consider  how  every  improvement  in  the  cul- 
ture medium,  so  far  as  this  organism  is  concerned,  tends  to  increase 
the  ease  of  its  isolation,  we  may  well  inquire  whether  our  present 
methods  of  recovery  give  us  an  adequate  idea  of  the  real  richness  of  the 
specimens  in  dysentery  bacilli.  In  only  one  case  (No.  16)  of  my  series 
did  the  number  of  dysentery  bacilli  appear  to  be  large  and  in  this  it  was 
considerably  below  the  number  of  colonies  of  non-dysenteric  bacilli 
which  grew  upon  the  plates. 

I  regret  that  the  pressure  of  work  prevented  me  from  making  a  study 
of  the  agglutinating  properties  of  the  blood  of  the  children  from  whom 
the  dysentery  bacilli  were  obtained.  This  test  was  made  in  a  few 
instances  but  as  it  couid  not  be  carried  out  regularly  I  did  not  pursue 
it  as  I  had  hoped  to  do.  I  was  impressed  by  Dr.  Flexner  with  the 
desirability  of  studying  with  thoroughness  the  distribution  of  dysen- 
tery bacilli  in  the  discharges  of  children  suffering  from  diarrhea  and 
hence  I  sacrificed  all  other  features  of  the  investigation  to  this  one. 
Moreover,  it  would  have  been  easy,  in  view  of  the  large  number  of 
cases  which  came  for  treatment  to  the  Floating  Hospital,  to  have  con- 
siderably enlarged  the  total  number  of  cases  examined.  But  here  again 
I  readily  coincided  with  his  view  that  thoroughness  of  investigation  of 
individual  cases  was  more  important  than  a  less  exhaustive  study  of 
a  larger  number  of  children. 

Since  my  study  has  been  so  uniform,  it  is  worth  while  to  inquire 


8o 


Arthur  I.  Kendall. 


oS 


(!) 

<u 

— 

= 

3 

2 

16 


16 
28 


32 


26 

16 

19 

8 

32 

56 


9 

16 

14 

32 

7 
35 

S 

9 
16 
40 
16 
17 
34 


U 


Type  of 

Bacilli. 


Description  of  Stool. 


Notes. 


+  + 


o  Green-yellow,  fluid;  blood  flecks 
Green-yellow,  fluid 

—  Green-yellow  formed 

Green-yellow;  mod.  mucus 
Formed  with  little  mucus 


o  Yellow-green  mucus 

—  j Green-yellow;  mod.  mucus 

—  'Scraping  from  intestine   post 

tem. 
+  Green-yellow;   much  mucus 
+  Bloody  mucus  and  feces 
+  'Yellow-green;   mod.  mucus 
+  Yellow-green;  little  mucus 

Yellow-green;  little  mucus 

Yellow-green;  mod.  mucus 

Blood  and  mucus 

Blood  and  mucus 


Cultures     from    intestinal 

post  mortem. 
Yellow-green;  mod.  mucus 
Yellow-green;  mod.  mucus 
Blood  and  mucus 
Yellow-green;  mod.  mucus 

Variable 


Dysentery       bacilli 
scarce. 


Dysentery       bacilli 
scarce. 


Large  number  of 
dysentery  bacilli 
present. 

Tuberculous  ileo- 
colitis. 


Proctitis. 

Dysentery 
scarce. 

Typhoid 
Many 
bacilli 


bacilli 

fever, 
typhoid 
isolated. 


Yellow-green;  mod.  mucus 
Yellow-green,  formed ;    mod.  mucus 
Greenish  fluid;  much  mucus 
Green-yellow,  formed  ;  little  mucus 


Blood  positive  to 
YVidal  test. 


Bacilli  nally 

bleached       milk. 


Solid,  brownish-black;    much  mucus 

Green-yellow,  semi-fluid;    mod.  mu-  Dvsentery 
cus  scarce. 

Green-yellow,  semi-fluid;    mod.  mu- 
cus 

Green-yellow,  semi-fluid;    much  mu- 
cus 

Green-yellow,  semi-fluid;    mod.  mu- 
cus 

Green-yellow,  semi-solid;    mod.  mu- 
cus 

Green-yellow,  semi-fluid;    mod.  mu-  Tuberculosis, 
cus 

Green-yellow,  semi-solid;    mod.  mu- 
cus 

Green-yellow,  semi-solid;    mod.  mu- 
cus 


bacilli 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  81 

whether  the  precise  character  of  the  discharges  greatly  influenced  the 
results.  If  the  table  is  scrutinized  it  will  be  observed  that  the  number 
of  plates  used  in  the  investigation  of  the  different  cases  varied  greatly, 
and,  if  it  is  recalled  that  the  cases  were  studied  in  series  of  8  plates 
per  examination,  some  notion  can  be  obtained  of  the  relative  ease  or 
difficulty  with  which  a  positive  result  was  achieved.  This  test  is  of 
course  not  absolute,  and  much  may  have  depended  on  accidental  cir- 
cumstances, but  taken  altogether  it  probably  is  the  most  reliable  one  at 
our  disposal  to  establish  the  variation  in  occurrence  of  the  bacilli. 

The  smallest  number  of  plates  studied  in  single  instances  were  in 
connection  with  cases  2,  3,  6,  9,  11,  16,  20,  23,  27,  29,  30  in  which 
from  7  to  10  plates  were  used.  Eliminating  case  20  which  was  negative, 
we  have  10  cases  yielding  the  bacilli  with  relative  ease.  Of  these  cases, 
blood  was  present  in  quantities  visible  to  the  naked  eye  in  one  case  only ; 
mucus  was  present  in  all  cases,  and  feces  in  all  but  two  cases.  On 
the  other  hand,  case  16  of  this  series  in  which  blood  occurred  yielded 
the  largest  number  of  dysentery  bacilli  of  all  the  specimens  examined. 

The  constant  abnormal  constituent  of  the  stools  was  mucus,  the 
quantity  and  appearance  of  which  were  subject  to  great  variations. 
Of  the  35  cases  investigated,  which  represent  the  entire  number  of  chil- 
dren ill  of  all  diseases,  the  discharges  in  all  contained  mucus,  while  in 
only  6  was  blood  discovered.  A  microscopical  study  of  the  dejecta 
with  a  view  of  determining  the  occurrence  of  extravasations  of  small 
numbers  of  red  corpuscles  was  not  made. 


REPORT   OF  PAUL  A.   LEWIS,   Stud.Med., 

Philadelphia. 

The  cases  studied  in  Philadelphia  occurred  in  parts  of  the  city 
widely  removed  from  one  another.  The  central  point  from  which 
materials  were  to  be  drawn  was  the  Children's  Hospital,  but  at  the 
critical  moment — during  the  height  of  the  hot  season — the  hospital 
was  closed  during  a  period  of  three  weeks  on  account  of  an  epidemic 
of  diphtheria.  I  was  therefore  obliged  to  depend  for  material  for 
study  upon  hastily  formed  associations  with  other  institutions.  Later 
on  in  the  season  the  Children's  Hospital  reopened  and  during  July  and 
August  a  number  of  specimens  was  obtained  from  that  source.  My 
work  in  Philadelphia  was,  however,  interrupted  and  finally  brought  to 
an  abrupt  close  through  my  transfer  first  to  Xew  York  and  then  to 
Boston  to  assist  in  the  investigations  which  were  being  conducted  in 
those  places.  Therefore,  the  number  of  cases  of  diarrheal  disease 
in  children  investigated  bacteriologically  in  Philadelphia  is  smaller  than 
it  would  have  been  but  for  the  interruptions  mentioned.  Perhaps  the 
total  results,  too,  are  different  from  what  they  might  have  been  had 
opportunity  been  afforded  to  follow  more  carefully  some  of  the  negative 
cases. 

I  am  indebted  for  the  material  for  my  study  to  the  following  physi- 
cians to  whom  I  wish  to  express  my  appreciation  of  many  kindnesses 
shown  me :  Drs.  Hand  and  YVieher,  of  the  Children's  Hospital ;  Dr. 
Hamill.  of  the  Polyclinic  Hospital;  Drs.  Griffiths,  Ostheimer  and 
Levy,  of  the  University  Hospital,  and  Dr.  Xewmayer  through  whom 
the  cases  in  the  tenement  district  came  into  my  hands. 

I  am  enabled  through  the  courtesy  of  the  physicians  in  charge  of  the 
cases  to  include  brief  clinical  descriptions  and  diagnoses  of  the  cases 
examined. 

METHOD   OF    WORK. 

Collection  of  Stools. — The  stools  were  taken  on  the  ordinary  nap- 
kins. Every  effort  was  made  to  get  the  discharges  as  soon  after  they 
were  passed  as  possible.  However,  in  the  earlier  half  of  the  summer — 
cases  i  to  15 — this  point  was  not  so  rigidly  insisted  on.     If  an  hour 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


83 


Diagnosis    and    Description. 


Acute   ileo-colitis:  severe  ;  sudden  onset  with  fever.     Slow  recovery 

Summer  diarrhea :  chronic  case  with  periodic  exacerbations  of 
severe  symptoms  ;  onset  in  late  winter;  patient  poorly  nourished 
and  debilitated 

Summer  diarrhea:  child  slightly  ill  ;  no  careful  examination  could 
be  made 

Acute  ileo-colitis  with  pneumonia  :  marked  toxic  symptoms.  Death 
end  of  first  week  ;    autopsy , 

Acute  ileo-colitis  with  pneumonia:  death  shortly  after  admission  ; 
autopsy  ;  mild  intestinal  lesions 

Summer  diarrhea — moderately  severe  and  persistent :  no  fever,  little 
prostration 

Gastro-enteritis:  moderately  severe,  later  became  chronic  and  fatal 
termination  expected 

Acute  ileo-colitis:  case  with  relapses  and  severe  intestinal  symptoms. 

Gastro-enteritis:  severe  diarrhea;  slight  constitutional  symptoms  and 
quick  recovery 

Ileo-colitis  with  pneumonia:   not  followed 

Gastro-enteritis:  chronic  case  with  severe  diarrhea 

Gastro-enteritis:  early  history,  suspected  intussusception;  late  re- 
lapses; chronic  course.  Autopsy:  pseudo-membranous  ileo-co- 
litis  

Ileo-colitis:  not  followed 

Ileo-colitis:  chronic  case — not  followed 

No  history 

Acute  ileo-colitis:  severe  case  with  fever  and  prostration ;   relapse... 

Ileo-colitis:  bloody  and  mucous  diarrhea  without  prostration  or  fever; 
not  followed 

Ileo-colitis:   no  history 

Ileo-colitis  with  pneumonia:  autopsy  showed  mild  intestinal  lesions 
and  extensive  pulmonary  consolidation 

Ileo-colitis:  chronic  case;   not  followed 

Ileo-colitis :  chronic  case ;  not  followed 


Bacteriological 
Result. 

+  =Pos. 

— =Neg. 


+  Early 


or  two  had  elapsed  before  the  specimen  was  obtained  it  was  still  used 
providing  no  later  one  was  available.  During  the  remainder  of  the 
summer  no  stool  was  taken  which  had  not  been  passed  within  the  hour 


84  Paul  A.  Lewis. 

and  great  effort  was  made  to  obtain  them  within  a  few  minutes  of  the 
time  of  passage.  At  first  the  napkins  were  carried  to  the  laboratory  and 
suspensions  were  made  there.  Later,  tubes  of  culture  medium  and  an 
alcohol  lamp  were  taken  and  suspensions  made  on  the  spot.  The  table 
which  follows  shows  the  time  elapsing  between  the  passage  of  the 
stools  and  the  plating : 


POSITIVE   CASES. 

NEGATIVE   CASES. 

Number. 

Elapsed  Time. 

Number.                   Elapsed    Time. 

Hours. 

2 

5 
3 

1 

4 
2 

1 
1 
1 

1 

5 
2 

... 

Minutes. 
30 

30 
30 

30 

15 
15 

30 
4 

Hours. 

3 

4 
4 
2 
2 
4 
4 
4 
1 
2 

4 
1 

Minutes. 

30 

6     

11      

H     

16     

18     . 

Minimum 

4 

Plating. — From  the  stool  when  obtained  I  made  suspensions  in 
salt  solution  or  bouillon.  The  mucus,  as  free  from  fecal  matter  as 
possible,  was  transferred  to  the  tubes.  When  blood  was  present  it 
also  was  admitted  to  the  suspension  but.  in  none  of  these  cases  was 
it  possible  to  plate  blood  alone  distinct  from  the  mucus.  At  first 
enough  mucus  was  transferred  (3 — 5  loops)  to  make  a  cloudy  suspen- 
sion after  shaking.  From  this  first  tube  6  loops  were  put  into  a  second 
suspension  and  from  this  tube  all  the  plates  were  made.  The  seeding 
was  varied  by  changing  the  number  of  loops  transferred  to  the  agar 
tubes.  The  best  plates,  as  a  rule,  were  those  which  contained  3 — 4  loops 
of  the  second  suspension.  Later  in  the  summer,  the  first  suspension 
was  made  so  light  that  when  it  had  settled  after  a  vigorous  shaking 
the  supernatant  fluid  was  not  clouded.  Then  1 — 2  loops  were  trans- 
ferred to  the  agar  tubes.  The  difficulty  was  to  get  the  right  amount 
of  material  suspended,  the  plates  at  first  being  always  too  thickly 
seeded.  In  several  cases  I  tried  washing  the  mucus  through  one  or 
two  tubes  of  sterile  water  to  free  it  from  all  fecal  matter.  In  the  first 
case  tried  in  this  way  a  surprisingly  larger  number  of  colonies  of  the 
dysentery  bacillus  developed  in  the  plates.     I  had  formed  great  hopes 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  85 

upon  this  variation  and  introduced  it  into  the  later  work,  but  I  did  not 
find  it  to  yield  results  which  were  better  than  those  given  by  the  first 
method  employed. 

The  plating  medium  was  1.5  per  cent,  agar-agar  made  with  beef 
extract  and  kept  slightly  but  distinctly  acid  to  litmus. 

Marking  and  Picking  Colonies. — I  followed  the  Vedder-Duval 
method  of  incubating  the  plates  and  marking  the  superficial  colonies 
after  12 — 24  hours  incubation.  In  the  early  summer  I  always  returned 
the  marked  plates  to  the  thermostat,  but  later,  after  my  fifth  case, 
I  made  it  a  rule  to  pick  about  30  colonies  of  the  first  crop.  On  the 
basis  of  my  summer's  work  I  can  form  no  satisfactory  estimate  of  the 
relative  advantages  of  the  two  procedures ;  but  I  can  affirm  the  possi- 
bility of  securing  colonies  of  B.  dysenteriae  among  the  results  of  this 
first  transplantation. 

The  great  variation  in  number  of  dysentery  colonies  recoverable 
from  the  plates  makes  any  rule  as  to  the  extent  of  the  picking  to  be 
followed  unreliable.  In  no  case  reported  as  negative  were  less  than 
150  colonies  transferred;  in  one  case  500  colonies  were  tested  with 
negative  results.  The  positive  cases  were  yielded  more  readily.  From 
the  plates  of  Case  VIII.  I  picked  in  all  35  colonies,  of  which  28  proved 
to  be  B.  dysenteriae.  I  have,  however,  in  one  instance,  taken  off  200 
colonies  to  secure  in  the  end  a  single  tube  of  the  dysentery  bacillus. 

Transplanting  Media. — At  the  beginning  of  the  summer,  glucose  agar 
was  used  as  the  medium  to  separate  gas-producers  from  the  non-gas- 
producers  in  glucose-containing  media.  This  medium  will  show  gas  for- 
mation in  12 — 24  hours  as  a  rule;  sometimes,  however,  it  is  delayed  for 
48  hours.  The  litmus  mannite-agar  can  also  be  used  for  this  purpose 
and  acts  more  quickly  and  unequivocally,  in  my  opinion,  besides  which 
it  serves  the  purpose  of  giving  a  primary  differentiation  of  the  two 
types  of  dysentery  bacilli  when  present.  But  the  difficulty  of  preparing 
the  medium,  where  such  large  quantities  are  to  be  used,  is  a  drawback. 
After  my  return  from  New  York  where  I  had  spent  10  days  with 
Duval  I  employed  exclusively  the  semi-solid  jelly  of  Hiss.  I  found 
this  medium  not  only  to  show  gas  production  quickly,  but  also  to  indi- 
cate motility  and  to  bring  out  a  fairly  characteristic  form  of  growth 
of  B.  dysenteriae. 

Subsequent  Procedures. — Having  adopted  the  Hiss  medium  as 
recommended  by  Duval  I  also  followed  his  method  for  the  demon- 
stration of  the  identity  of  the  bacillus  of  dysentery  by  studying  di- 
rectly from  this  medium  the  morphology  and  agglutinative  properties 
of  suspected  organisms.     Next,  the  organisms  were  transferred  to  the 


86 


Paul  A.  Lewis. 


litmus-milk  and  litmus  mannite-agar  media.  From  this  point  on,  the 
identification  of  the  organism  and  differentiation  of  types  offer  no 
difficulties.  I  followed  the  usual  methods  pursued,  paying  strict  atten- 
tion to  the  changes  occurring  in  the  milk  medium. 


RESULTS    OF    THE    STUDY. 


Of  the  21  cases  examined,  n  yielded  positive  and  10  negative  bac- 
teriological results  so  far  as  the  bacillus  of  dysentery  was  concerned — 
in  other  words,  the  organism  was  isolated  from  stools  in  52.5  per  cent, 
of  the  cases. 


u   en 


29 
18 


18 

21 

18 
30 
26 

28 
27 
15 
30 
30 

20 

21 
18 
2? 
24 
28 

27 


U-oS 
oqq| 

r-    Ifl    ~ 
C     U    V 

Z  o  v 


16 

J4 
28 

9 


Type  of 

Bacilli 


16 


28 
9 


«4 


o;g 


I  :4<D 


Brief  Description  of  Stool  Examined. 


S.   Blood-flecked  mucus 

S.   Large,   curdy;    fecal,  with  rr 

blood  flecks 
S.   Formed  fecal   with    little    mucus   but  T.  D. 

much  blood 
S.  Mucus  flecked  with  blood 
S.   Large,  cheesy  and  fecal;  little  mucus 
S.  Undigested  food  with  mucus 
S.   Some  feces  with  much  mucus 
S.   Scanty;  bloody  mucus  with  feces 
S.   Large;    muco-fecal 
S.   Curds  and  feces;    little  mucus 
S.   Much  feces,  little  mucus 
S.   Scanty;    mucus  and  feces 
S.   Scanty;  green  mucus  with  feces 
S.   Curds  and  mucus 
S.   Curds  and  little  mucus 
S.  Scanty;  muco-fecal 

S.   Large;  mucous  and  fecal;  blood  streaks  T 
S.   Muco-fecal  with  blood  flecks  C. 

S.   Large;  muco-fecal  C. 

S.  Curds,  mucus  and  feces  C. 

S.  Large;  muco-fecal  JC. 


'U. 
and  T. 


H. 
H. 
D. 
H. 
D. 
D. 
H. 
H. 
H. 
H. 
H. 
3.S 
H. 
D. 
H. 
H. 
H. 
H. 


U.  H.  =  University  Hospital.       T.  D.=Tenement   district.      P.    H.  =  Polyclinic     Hospital. 
C.  H.=Children's  Hospital.     R.  B.  S.  =  Red  Bank  Sanitarium. 


As  to  types,  the  bacillus  which  I  recovered  was  in  8  cases  the  "Flex- 
ner-Harris"  and  in  3  cases  the  "Shiga"  organism.  In  no  case  were  both 
types  of  bacilli  found  associated. 

The  agglutination  reactions  of  the  bacilli  isolated  and  identified  as 
the  bacilli  of  dysentery  were  tried  with  anti-dysenteric  serum  from  the 
horse.     These  reactions  were  positive,  although  in  the  case  of  certain 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  87 

bacilli,  subcultivations  were  needed  to  bring  out  a  good  reaction.  The 
best  results  were  obtained  through  the  use  of  serum  having  an  origin 
agreeing  with  the  type  of  the  bacillus,  but  cross-agglutinations  were 
also  obtainable.  Very  few  tests  were  made  with  the  blood  of  patients, 
as  it  was  found  very  difficult  to  secure,  under  the  conditions  in  which 
I  worked,  sufficient  blood  for  accurate  examination. 

In  conclusion,  I  should  like  to  state  that  as  I  look  back  upon  my 
results  through  the  experience  I  gained  later  in  the  summer  in  New 
York,  with  Duval,  and  in  Boston,  with  Kendall,  I  am  inclined  to  con- 
sider that  many  of  the  cases  reported  by  me  as  negative  were  in  reality 
examples  of  dysentery  bacillus  infection,  and  that  better  conditions 
of  work  and  doubtless  also  more  experience  on  my  part,  would  have 
caused  many  of  them  to  yield  a  part  of  their  content  of  the  bacillus  of 
dysentery. 


REPORT   OF   V.   H.   BASSETT.   M.D.. 
Baltimore. 

The  entire  number  of  cases  studied  was  73,  in  51,  of  which  or  70 
per  cent.,  the  dysentery  bacillus  was  found.  The  materials  employed  in 
the  51  positive  cases  consisted  of  the  discharges  from  the  intestine  in 
44  and  mucus,  etc..  obtained  directly  from  the  bowel  in  7  instances. 

The  discharges  contained  invariably  mucus,  although  the  amount  was 
subject  to  great  variation.  The  table  gives  an  approximate  estimate 
of  the  quantity  present  in  each  instance.  Blood  was  less  frequently 
present,  being  noted  in  24  cases.  In  other  words,  in  nearly  one-half 
of  the  examples  of  infection  with  B.  dysenteric  blood  in  quantities 
visible  to  the  naked  eye  was  absent.  In  quantity  the  blood  also  varied 
considerably  and  oftenest  occurred  in  the  form  of  points  and  small 
streaks — so-called  flecks.  Feces  were  noted  12—14  times  as  forming 
a  portion  of  the  material  used  for  the  cultivation  of  the  bacillus. 

The  number  of  colonies  of  the  dysentery  bacillus  taken  off  the  plates 
varied  within  wide  limits.  In  a  few  instances  one  or  two  colonies 
only  were  obtained,  and  the  majority  of  the  cases  yielded  small  num- 
bers of  colonies.     Just  what  interpretation  is  to  be  placed  upon  this 

[Editor's  Xote  :  Dr.  Bassett's  studies  were  carried  out  at  the  Wilson  Sani- 
tarium near  Baltimore  and  extended  through  the  summer  months  of  1903.  The 
report  supplied  by  Dr.  Bassett  consists  of  the  records  of  the  cases  studied  and  a 
letter  in  which  these  are  briefly  reviewed.  The  following  report,  which  I  have 
constructed  upon  the  basis  of  the  records  and  letter,  would  seem  to  cover  all  the 
points  which  are  essential;  but  I  am  sure  that  had  Dr.  Bassett  written  the  report 
he  would  have  presented  features  of  interest  which  through  ignorance  I  cannot 
do.  At  this  distance  (Germany)  and  in  view  of  the  brief  time  at  my  disposal  for 
completing  the  series  of  reports  on  the  summer's  work,  I  am  unable  to  communi- 
cate with  Dr.  Bassett  so  as  to  secure  a  personal  report  which  should  be  ready  for 
immediate  publication.  Fortunately  his  records  are  minute  and  full  so  that  no 
doubt  exists  as  to  their  significance.  I  find  myself  regretting,  however,  one  omis- 
sion that  I  wish  might  be  supplied,  namely,  a  statement  of  the  method  pursued 
by  him  for  isolating  the  bacillus  of  dysentery.  Since  he  says  nothing  about  this 
matter  I  am  led  to  suppose  that  he  has  not  departed  in  the  main  from  the  method 
employed  by  him  and  Duval,  the  previous  summer,  which  is  essentially  that  used 
by  Tedder  and  Duval.  Mention  is,  however,  made  that  the  discharges  were  col- 
lected upon  sterile  gauze  pads. — Simon  Flexxer.] 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  &9 

fact  is  not  evident.  That  the  materials  used  for  the  plating  play 
an  important  part  will  later  become  clear,  and  it  seems  highly  probable 
that  the  best  method  at  present  at  our  disposal  for  isolating  the  bacillus 
leaves  much  to  be  desired. 

The  absence  of  relationship  between  the  number  of  plates  poured  and 
the  number  of  colonies  of  B.  dysenterise  recovered  is  easily  accounted 
for.  The  entire  series  of  plates,  even  when  this  is  small,  may  not  be 
gone  through  minutely.  If  success  attends  the  early  picking  of  colonies 
no  further  use  is  made  of  the  plates,  and  it  is  only  in  the  cases  in  which 
difficulty  of  isolation  is  experienced  that  the  full  number  of  plates  is 
closely  studied. 

There  is  undoubtedly  a  fluctuation  from  time  to  time  in  the  number 
of  dysentery  organisms  thrown  off  with  the  discharges  or  recover- 
able in  them.  In  nine  cases  (4,  5,  9,  10,  26,  2?,  45,  47.  48)  more  than 
a  single  examination  was  made  and  in  one  instance  only  in  each  case, 
was  the  dysentery  bacillus  secured.  In  at  least  one  instance  (Case  8) 
the  number  of  bacilli  present,  at  the  time  of  successful  cultivation,  ap- 
pears to  have  been  quite  considerable,  and  in  another  (27)  after  a  suc- 
cessful cultivation  from  a  stool,  a  subsequent  scraping  from  the  rec- 
tum after  death  gave  negative  results. 

On  the  other  hand,  the  second  and  third  trials  may  exceed  the  first 
in  the  number  of  colonies  recovered.  In  all,  19  cases  were  studied 
more  than  once  with  positive  results.  I  will  give  a  few  illustrative 
examples: — Case  12:  1st  plating,  5  colonies;  2d  plating,  16  colonies; 
3d  plating,  8  colonies;  4th  plating,  10  colonies.  Case  38:  1st  plating, 
9;  2d,  26  (these  two  plated  on  same  day  using  separate  stools)  ;  3d, 
3  colonies.  Case  39  :  1st  plating,  48 ;  2d,  3  ;  3d,  20;  4th,  6  colonies,  all  on 
the  same  day  from  different  stools.  The  importance  of  repeated  ex- 
amination in  inconclusive  cases  as  well  as  the  bearing  of  the  fluctuation- 
factor  is  well  brought  out  by  these  figures. 

In  several  cases  in  which  the  stools  were  negative  the  examination  of 
material  derived  directly  from  the  intestine  gave  the  bacillus  of  dysen- 
tery. Thus  stools  from  Case  9  were  examined  on  June  26th  and  30th 
without  yielding  the  bacilli ;  while  a  scraping  from  the  rectum  taken 
on  July  4th  yielded  two  colonies  of  the  organism.  Case  20,  having 
failed  to  yield  the  bacillus  from  a  stool  and  from  mucus  obtained 
through  the  passage  of  a  rectal  tube,  a  scraping  from  the  mucosa  at 
autopsy  gave  a  positive  result.  Case  21  had  been  examined  twice  nega- 
tively (stools)  and  once  positively  (rectal  scraping)  during  life.  At 
the  autopsy,  cultures  were  obtained  from  the  mucosa  of  the  colon  and 
an  ulcerated  Peyer's  patch. 


9°  V.  H.  Bassett. 

That  the  bacillus  of  dysentery  is  more  readily  recovered  from  the 
mucosa  of  the  intestine  than  from  the  discharges  follows  from  what 
has  been  stated  upon  that  subject;  but  the  fact  is  also  proven  by  the 
rare  failures  that  follow  the  employment  in  cultures  of  portions  of  the 
mucous  membrane  or  the  mucus  derived  immediately  from  the  patho- 
logical tissue.  We  were  almost  uniformly  successful  in  obtaining  the 
dysentery  bacilli  from  all  the  cases  that  came  to  autopsy  and  from  a 
number  m  which  rectal  scrapings  were  carried  out  during  life  in  which 
the  stools  had  failed  to  yield  the  organism.  In  one  case  only  (27)  did 
a  post  mortem  rectal  scraping  give  negative  results  although  in  two 
additional  cases  (2  and  13)  in  which  the  material  was  obtained  directly 
from  the  bowel  during  life,  failures  were  recorded.  In  7  autopsies  the 
bacilli  were  recovered  from  the  intestines.  In  one  instance,  case  14,  the 
bacilli  were  obtained  from  a  stool  on  August  19th,  whereas  they  were 
missed  in  the  post  mortem  scraping  taken  3  days  later.  In  the  latter 
set  of  plates  innumerable  streptococci  developed. 

The  bacillus  of  dysentery  and  streptococci  in  large  numbers  may  exist 
side  by  side  on  the  plates  without  preventing  each  other's  development. 
Thus  we  noted  the  association  of  streptococci  in  small  or  moderate 
numbers  with  the  dysentery  bacillus  in  many  cases,  and  in  very  large 
numbers  in  14  cases  from  which  the  bacillus  was  secured.  While  this 
association  may  be  of  considerable  clinical  significance,  it  is  not  op- 
posed to  the  isolation  of  the  bacillus  of  dysentery  in  cultures. 

Case  51  yielded  a  good  number  of  colonies  of  B.  dysenteriae,  but 
is  interesting  chiefly  as  bringing  out  the  contagious  nature  of  the  diar- 
rhea from  which  the  child  suffered.  In  the  family  to  which  this  child 
belonged  three  cases  of  diarrhea  developed.  The  first  case  occurred 
sporadically  and  then,  after  an  interval  of  a  few  weeks,  a  second,  and 
10  days  later,  a  third  case  appeared. 

Some  attention  was  paid  to  the  reaction  of  agglutination,  the  blood 
of  the  sick  children  being  used  in  making  the  tests.  Agglutinations 
were  the  rule  in  cases  in  which  the  bacilli  were  present  (see  table)  and 
in  degree  they  not  uncommonly  reached  a  dilution  of  1  :iooo  to  1  :150c 
Still  there  were  notable  exceptions  to  this  rule  for  which  no  explanation 
is  at  hand.  The  cases  which  gave  negative  results  in  the  bacteriological 
study  yielded  far  fewer  positive  reactions  of  agglutination.  Since  it 
is  possible  in  a  given  instance  to  fail  to  secure  the  dysentery  bacillus 
from  an  otherwise  suspicious  case  of  diarrhea,  I  am  disposed  to  regard 
a  high  agglutination  as  indicating  infection  with  that  bacillus.  Un- 
fortunately the  contrary  is  not  true,  for  absence  of  the  reaction  does 
not  exclude  either  the  infection  or  failure  to  recover  the  specific  bacillus. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


9i 


POSITIVE  CASES. 


1) 
X! 

E 

D 

a! 

0  i 

offl 

Type  of 

Colonies. 

c 
0 

7, 

c 
0 

0 
J. 

Description  of   Mate- 
rial   Used     for 

Agglutination 
of  Blood. 

0    ■ 

en  -a 

.2  $ 

- 

Termina- 

3 

3-h     V] 

u  vn      . 

.2 

*■ 

a 

.5 

c 

Cultures. 

V 

V 

> 

Qh 

tion. 

£ 

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« 0  « 

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3 

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be 

V 

O  T3 

0) 

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C    w    *-i 

CUD 

3  '3  ■£ 

a! 

in 

c 

c 

3 

u 
11 

S.=Stool. 

'53 

0 

U 

?; 

f-*   O  a> 

- 

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fc, 

Oh 

£ 

Dm 

1 

12 

3 

3 

0 

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Scraping  from   colon 
post  mortem. 

i :  i,oco 

28 

Death. 

2 

12 

3 

3 

0 

0 

+ 

+ 

S.  Yellow;    muco-fe- 
cal 

1 :  20 

17 

Not  stated. 

3 

12 

4 

4 

0 

0 

+ 

+ 

S.  Muco-fecal 

1 :  100 

9 

Death. 

4 

8 

3 

3 

0 

0 

+ 

0 

S.  Scanty, green  ;  mu- 
co-purulent. 

1 : 1,000 

17 

Not  stated. 

5 

8 

3 

3 

0 

0 

+ 

+ 

S.   Muco-fecal;    mod. 
mucus 

1 : 1,000 

16 

Not  stated. 

6 

12 

15 

15 

0 

+ 

+ 

0 

S.  Scanty,  muco-pur., 
with  flecks  of  blood 

1 :  20 

22 

Not  stated. 

7 

24 

3 

3 

0 

0 

+ 

+ 

S.  Mucus  with  much 
feces 

1 :  100 

16 

Not  stated. 

8 

11 

25 

25 

0 

+ 

+ 

4- 

S.     Large,     muco-fe- 
cal with  blood 

Not  stated. 

9 

12 

2 

2 

0 

— 



— 

Rectal  scraping   dur- 
ing life 

1:50 

9 

Not  stated. 

10 

20 

4 

4 

0 

+ 

+ 

4- 

S.   Yellow  muco-pur. ; 
blood      microscopi- 
cal 

Not  stated. 

u 

20 

4 

4 

0 

+ 

4- 

O 

S.  Scant;   green  mu- 
cus; flecks  of  blood 

1 :  20 

20 

Not  stated. 

1  a 

6 

5 

5 

0 

+ 

+ 

O 

S.     Muco-pur.,      with 
blood  flecks 

1 :  20 

33 

Not  stated. 

13 

14 

4 

4 

0 

0 

+ 

O 

S.  Curdy ;  mucus  and 
pus 

Not  stated. 

14 

8 

8 

8 

0 

+ 

+ 

O 

S.  Muco-pur.,  bloody 

1:  1,500 

? 

Death. 

*5 

12 

2 

2 

0 

+ 

+ 

O 

S.  Much  mucus;  blood 
flecked 

Not  stated. 

16 

12 

14 

14 

0 

+ 

+ 

O 

S.   Muco-pur.;     with 
blood  flecks 

Not  stated. 

'7 

16 

30 

30 

0 

0 

+ 

O 

S.   Muco-purulent 

Not  stated. 

18 

12 

7 

7 

0 

— 



Rectal    scraping  dur- 
ing life 

1 :  20 

4 

Not  stated. 

19 

12 

5 

5 

0 

0 

+ 

4- 

S.    Large ;    muco-fe- 
cal 

1:50 

20 

Not  stated. 

21  > 

6 

47 

47 

0 

— 





Scrapings  from  colon 
p.m. 

1 :  20 

Death. 

21 

12 

10 

10 

0 

— 



~ 

Rectal   scraping  dur- 
ing life 

1 : 1,000 

? 

22 

12 

36 

36 

0 

+ 

+ 

O 

S.  Green  ;          blood- 
stained muco-pus 

Not  stated. 

23 

12 

23 

23 

0 

+ 

+ 

O 

S.   Bright  red;  bloody 
mucus 

1 : 1 ,000 

Not  stated. 

24 

12 

2 

2 

0 

0 

+ 

O 

S.  Scant,  green;  mu- 
cus 

1 :  100 

Not  stated. 

25 

12 

1 

1 

0 

+ 

+ 

O 

S.   Fluid,  muco-pur.; 

1 :  100 

Not  stated. 

# 

blood  flecks 

26 

8 

2 

2 

0 

0 

+ 

0 

S.   Muco-purulent 

1:500 

Not  stated. 

27 

18 

3 

3 

0 

0 

+ 

O 

S.  Watery,    greenish 
mucus 

1 :  1 ,000 

3 

28 

24 

5 

5 

0 

0 

+ 

4- 

S.  Abundant      green 
mucus,    yellow    fe- 
ces 

1 :  100 

29 

10 

8 

8 

0 

- 

+ 

O 

S.  Green  mucus  with 
little  blood 

1:  1,000 

3 

30 

18 

10 

10 

0 

+ 

+ 

O 

S.  Green  ;   muco-pus 
with  little  blood 

1 :  20 

? 

*  Larger  number  of  organisms  secured  at  other  platings. 


92 


V.  H.  Bassett. 


POSITIVE  CASES.     (Continued.) 


3i 
32 
33 
34 
35 

36 

37 

38 

39 

40 

41 
42 

43 

44 

45 
46 

47 
48 

49 

50 
51 


18 
18 
15 
15 

6 
24 


7 

24 

9 


24 

24 

24 
24 
15 


O-o 

oPQ 

c    w   t- 

C    ill    u 

^    O    <D 


Type  of 

Colonies, 


9 
48 


81 

3 
4 
4 
3 

4 

5 


Description  of   Mate- 
rial  Used    for 
Cultures. 

S.=  Stool. 


Rectal   scraping  dur- 
ing life 
S.  Small  mucus  blood 

stained 
S.   Fecal  with  bloody 

mucus 
S.  Scanty;    muco-pus 

and  blood 
S.   Mucus  with  blood 

staining; 
S.  Mucus  and  blood 
Rectal  scraping  dur- 
ing life 
S.  Mucus  and  blood 
S.   Blood-stained  mu- 
co-pus 
S.   Mucus 

S.   Mucus  and  curds 
S.  Curds,   feces,  mu- 
co-pus, blood 
S.  Scanty;  green  mu- 
co-pus and  curds 
S.  Small  mucus 
S.  Small  mucus 
S.  Scanty;  muco-pur. 
S.  Small   mucus  and 

fecal 
S.  Green  mucus  and 
curds 

Muco-pus         and 
blood 
S.  Mucus  and  feces 
S.    Muco-pus         and 
blood 


Agglutination 

of  Blood. 

c8 

be 

0 

<u 

a. 

Z 

1 :  1,000 


1:  1,000 

1:1,000 

i;  1, coo 
1  :  250 
1  :  100 


:  250 

200 


OT3 


:50 


:50 


Termina- 
tion. 


As  regards  the  duration  of  the  reaction  I  would  record  merely  the  two 
instances  (50,  51)  in  which  the  blood  was  still  active  three  months  after 
recovery  from  diarrheal  disease. 

(Bassett  writes  of  the  cases  in  which  he  failed  to  isolate  the  dys- 
entery bacillus:  "Of  the  negative  cases  many  were  undoubtedly  ex- 
amples of  infection  with  the  dysentery  bacillus.  In  some  the  organism 
was  missed  either  because  of  simple  failure  to  recover  it  or  by  reason 
of  failure  to  follow  the  cases  promptly  in  the  rush  of  work  which  came 
about  the  18th  of  July.  After  arrangements  were  made  which  insured 
a  steady  supply  of  culture  media  I  missed  few  cases.  On  the  other 
hand,  the  negative  group  includes  a  number  of  examples  which  I 
think  were  clearly  not  infections  with  the  bacillus  of  dysentery;  these 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 

NEGATIVE  CASES. 


93 


oS 


£~ 


24 
15 


Description  of  Material  Used 
for  Cultures. 

S.=Stool. 


Agglutination 
of    Blood. 


+ 
+  1  o 


S.    Scanty  mucus  and  fecal 

Rectal  scraping  during  life 

S.      Fluid,      fecal      with     green 

mucus  and  pus 
S.    Green      mucus     and      white 

muco-pus 

S.  Much  brown  fluid  feces  with 
mucus 

S.  Green  curds,  feces  and  mu- 
cus 

S.    Scanty  mucus 

S.    Green  muco-pus 

S.    Abundant  green  mucus 

S.    Muco-pus  and  curds 

S.    Muco-pus  and  blood-flecks 


S.    Mucopurulent 


Rectal  scraping  during  life 

S.    Yellow,  fluid;  muco-pus  and 

feces 
S.    Fecal  with  little  mucus 

S.    Small,  pasty  muco-purulent 
S.    Fluid,     yellow    with     green 

mucus 
S.    Green  mucus 
S.    Small,  green  mucus 

S.    Fecal  with  mucus 

S.    Small,  green  mucus 

S.    Small,  green  mucus 


1:50 


1:500 


1:50 
1:50 
1:50 

1  150 
1:50 
[ :  20 
1:50 

1:50 


1:50 
1:50 


in  XJ 

«  v 

.SI 

o-a 


17 

17 
? 

15 

? 
26 


24 
29 


29 


18 


Notes. 


Plates  not  marked  and 
only  eight  colonies 
subcultured 

Examined  during  con- 
valescence. 

Plates  poorly  seeded. 

Second  test  plates 
heavily  seeded  and 
failure.  Streptococ- 
ci numerous. 


Two    sets     of    plates 

made. 
One    'specimen      only 

secured. 

Few  subcultures  from 
plates  made. 

Few  subcultures  from 
plates  made. 

Few  subcultures  from 
plates  made.  Sec- 
ond specimen  could 
not  be  obtained. 

Plates  overgrown  with 
B.  proteus.  Sec- 
ond .specimen  not 
obtained. 

Stool  also  negative. 


Streptococci  numer- 
ous. 

Second  plates  also 
negative. 

Numerous  strepto- 
cocci 

Second  plates  also 
negative. 

Two  other  stools 
negative. 

Second  plates  also 
negative. 


were  cases  of  mucous  diarrhea  of  other  origin."  As  regards  the  strepto- 
coccus Bassett  states :  "I  am  also  convinced  that  the  streptococcus 
is  concerned  in,  and  is  at  least  a  cause  of  secondary  infection.") 


THE    PATHOLOGICAL    ANATOMY    OF    SHIGA    BACILLUS 
INFECTION  OF  THE  INTESTINE  IN  INFANTS. 

BY    JOHN    HOWLAND,    M.D., 
Pathologist  to  the  New  York  Foundling  Hospital. 

(From  the  Laboratory  of  the  Babies'   Hospital,  Oct.,   1903.) 

The  Bacillus  dysenteries  (Shiga),  first  proved  by  Shiga1  to  be  the 
cause  of  the  epidemic  dysentery  of  Japan,  has  been  shown  by  the  work 
of  Flexner,  Kruse,  Miiller,  Deycke  and  others  to  stand  in  direct  causal 
relation  to  the  dysenteries,  epidemic,  endemic  and  sporadic,  of  the 
tropical  and  temperate  zones,  and  its  etiological  importance  is  now  uni- 
versally recognized. 

The  pathological  lesions  in  adults  induced  by  infection  with  this 
bacillus  were  briefly  stated  by  Shiga2  to  be  more  superficial  than  those 
caused  by  the  amoeba  coli,  and  he  noticed  that  while  the  mesenteric 
glands  were  regularly  enlarged  the  spleen,  unless  some  complication 
was  present,  was  unaffected. 

Flexner3  reports  briefly  the  autopsies  of  three  cases  in  Manila,  the 
lesions  consisting  in  swelling,  congestion  and  slight  hemorrhage  into 
the  mucous  membrane,  with  slight  exudation  on  the  surface  in  one 
case  and  very  small  ulcerations  in  another.  He  states  that  histologically 
"the  changes  appear  in  the  mucous  membrane,  submucosa  and  mus- 
cularis,  being  most  marked  in  the  former  situations.  Those  of  the 
mucous  membrane  consist  of  coagulative  necrosis,  with  exudation  of 
fibrin  and  polymorphonuclear  cells.  .  .  .  The  pseudo-membrane  is 
a  close-meshed  network  of  fibrin  enclosing  multinuclear,  often  frag- 
mented cells.  .  .  .  The  submucosa  is  always  much  altered.  .  .  . 
Here  are  found  hemorrhages  of  variable  size,  while  in  the  interstices 
of  the  tissue  some  fibrin  appears.  More  marked,  however,  are  cellular 
accumulations  which  are  present,  not  uniformly,  but  in  irregular  areas. 
.  .  .  The  character  of  the  cellular  exudate  is  quite  uniform.  Ex- 
cluding the  red  blood  cells,  the  new  cells  consist  chiefly  of  plasma 
cells.  ...  In  the  submucosa,  infiltration,  hemorrhage  and  fibrin 
formation  take  place  also  beneath  an  intact  or  almost  intact  mucous 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  95 

membrane.     .     .     .     The    muscular    coat    shows    only    hemorrhages. 
.     .     .     The  peritoneal  tunic  is  usually  unaltered." 

He  emphasizes  the  fact  that  the  polymorphonuclear  leucocytes  play 
a  very  insignificant  role  in  the  process  of  infiltration  in  the  submucosa, 
whereas  in  the  affected  mucous  membrane  they  are  much  in  evidence. 
The  bacteria  were  abundant  in  the  fibrinous  exudation  on  the  mucous 
membrane  and  in  the  necrotic  tissue ;  he  could  not  find  them  in  the 
unaffected  tissue  and  believed  the  changes  in  the  submucosa  to  be 
toxic  in  origin. 

Strong  and  Musgrave4  gave  a  summary  of  the  changes  observed  in 
many  autospies  performed  by  them  in  Manila.  They  found  the  changes 
mostly  in  the  large  intestine  but  extending  usually  for  a  variable  dis- 
tance into  the  ileum.  The  whole  wall  of  the  intestine  was  thickened. 
The  superficial  part  of  the  mucosa  was  necrotic  and  usually  hemor- 
rhages were  found  beneath  this.  The  solitary  follicles  were  swollen 
and  red.  In  the  very  acute  cases  no  definite  ulceration  was  observed, 
but  only  a  general  superficial  necrosis  of  the  mucosa.  Microscopically 
there  was  necrosis  of  the  mucous  membrane,  with  distention  of  the 
blood  vessels  and  extravasation  of  blood.  An  extensive  cellular  infil- 
tration of  the  mucosa  was  the  rule,  and  there  were  hemorrhages  into 
the  submucosa  and  edema  of  the  same.  Plasma  cells  were  increased, 
especially  around  the  blood  vessels.  Edema  was  found  even  in  the 
muscular  coats.  The  mesenteric  glands  were  uniformly  much  enlarged. 
Bacilli  of  typhoid-colon  form  and  staining  properties  were  found  in 
the  mucosa,  and  cocci  often  mixed  with  them,  and  though  the  latter 
were  only  superficially  situated  the  bacilli  were  found  sometimes  not 
only  in  the  mucosa  but  all  through  the  areolar  tissue,  the  muscularis 
mucosas  and  submucosa  down  to  the  muscular  coats.  In  the  other 
organs  were  no  constant  changes.     No  mention  is  made  of  fibrin. 

Duval  and  Bassett5  in  a  preliminary  paper  first  pointed  out  the  rela- 
tionship between  the  B.  dy sentence  (Shiga)  and  the  summer  diarrheas 
of  infants.     They  studied  forty-two  positive  cases. 

Wollstein6  reports  the  finding  of  the  bacilli  in  thirty-nine  cases  of 
infantile  diarrhea  during  the  winter  months,  out  of  one  hundred  and 
fourteen  studied,  but  many  of  the  negative  cases  were  in  normal  chil- 
dren and  in  all  cases  having  blood  and  mucus  in  the  stools  the  bacilli 
were  present. 

Numerous  other  cases  in  addition  have  been  reported  and  the  B.  dys- 
enteries (Shiga)  is  now  generally  accepted  as  the  cause  of  the  majority 
of  the  various  forms  of  diarrhea  in  children. 

The   apparent   discrepancies  in  the   different  types   of   cultures   ob- 


9  6  John  Howland. 

tained  from  various  sources  have  partly  disappeared  in  die  light  of 
the  observations  of  Martini7  and  Lenz\  who  showed  by  reactions  and 
cultural  characteristics  that  there  are  at  least  two  types  of  this  organ- 
ism, known  to  us  as  the  true  Shiga,  not  fermenting  mannite,  and  the 
"Flexner-Harris,"  fermenting  mannite.  The  latter  of  these  is  the 
type  chiefly  found  connected  with  infantile  diarrhea  in  Xew  York, 
according  to  Wollstein,  only  one  of  her  positive  cases  being  of  the 
true   Shiga  type. 

Gay  and  Duval9  have  recently  reported  three  cases  in  adults  in 
which  both  types  of  the  organism  were  found,  in  one  case  the  acid- 
producing  or  "Flexner-Harris"  type  predominating,  in  another  the 
alkaline  or  true  Shiga  type,  and  in  a  third  the  number  of  positive  tubes 
were  approximately  the  same.  Xo  cases  of  double  infection  in  infants 
have  as  yet  been  found.* 

The  autopsies  whose  findings  I  wish  to  report  took  place  at  the  Xew 
York  Foundling  Hospital,  the  Babies'  Hospital  and  the  Nursery  and 
Child's  Hospital. 

The  organism  was  proved  to  be  present  in  the  great  majority  of 
cases  by  an  examination  of  the  stools,  but  in  seven  cases  it  was  ob- 
tained post-mortem  by  scraping  the  mucous  membrane  of  the  colon, 
and  in  three  cases  it  was  obtained  both  ante-mortem  and  post-mortem. 

The  organism  found  in  these  cases  corresponded  in  all  particulars 
to  the  type  known  as  the  acid-producing  or  "Flexner-Harris"  organ- 
ism; that  is.  it  did  not  ferment  glucose,  saccharose  or  lactose,  but  did 
split  mannite  with  acid  formation.  It  produced  an  early  acidity  in  milk 
with  a  subsequent  alkalinity  and  agglutinated  with  the  "Harris"  serum 
in  high  dilutions. 

The  autopsies  were  obtained  as  soon  as  possible  after  death,  the 
pieces  of  the  organs  placed  in  equal  parts  of  95  per  cent,  alcohol  and 
to  per  cent,  formalin.  After  from  one  to  three  days  they  were  trans- 
ferred to  alcohol  and  mounted  and  cut  in  paraffin.  The  staining  was 
done  with  hsemalaun  and  eosin,  sections  for  bacteria  were  stained  by 
the  Gram-Weigert  method  and,  for  those  negative  to  Gram,  with 
borax-blue  and  differentiated  with  )/2  per  cent,  acetic  acid.  The  Wei- 
gert  stain  for  fibrin  was  used  to  demonstrate  fibrin. 

The  first  seventeen  cases  were  winter  cases  occurring  between  X~o- 
vember  1st  and  April  15th,  and  the  last  fifteen  summer  cases,  between 
May  1st  and  September  1st.  There  seems  to  be  no  difference  in  the 
histological  findings,  due  to  the  time  of  year. 

*This  statement  was  true  at  the  time  it  was  written,  but  since  then  at  least  six 
cases  of  double  infection  in  infants  have  been  reported. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  97 

Report  of  Cases. 
Case  I. — C.  S.,  ten  and  one-half  months  old.  Brought  to  the  hospital  and 
left  without  any  history  being  obtained.  Signs  of  broncho-pneumonia  in  both 
lungs.  She  did  well  with  this  and  was  apparently  convalescent  when,  on  the 
eighth  day  after  admission,  she  began  to  vomit  and  have  frequent  mucous  and 
bloody  stools.  These  persisted  till  death,  seven  days  later.  Temperature  at 
first,  100-101.50  F. ;  rose  three  days  before  death  to  102-1030  F.,  where  it  re- 
mained. The  B.  dysentcrice  was  cultivated  from  the  stools  five  days  before  death. 
Autopsy. — There  is  a  typical  broncho-pneumonia  in  both  lungs,  degenerated 
kidneys,  a  large,  soft  hyperplastic  spleen  and  a  moderately  fatty  liver.  Stomach 
normal  as  also  small  intestine,  except  for  a  slight  follicular  hyperplasia.  The 
mucous  membrane  of  the  large  intestine  is  congested  throughout,  and  has  lost 
its  velvety  appearance,  but  there  is  no  thickening  of  the  wall. 

Microscopical. — There  is  a  marked  hyperplasia  of  the  lymphoid  follicles  in 
the  small  intestine  due  chiefly  to  an  increase  in  the  lymphoid  cells  and  less  to  an 
increase  in  the  endothelioid  cells.  The  hyperplasia  extends  into  the  surface 
mucosa,  separating  the  crypts  from  each  other,  and  densely  infiltrating  the 
stroma.  Here  there  are  occasional  depressions  in  the  mucosa  extending  into 
the  enlarged  follicles,  at  which  points  the  mucous  membrane  is  deficient.  The 
submucosa  is  quite  normal.  A  similar  hypertrophy  of  the  solitary  follicles  is 
found  in  the  large  intestine,  with  superficial  epithelial  defects  but  without  reac- 
tion. 

Bacteria. — There  are  few  organisms  in  the  sections,  either  positive  or  nega- 
tive to  Gram,   and  those  seen  are   very  near  the   surface. 

Case  II. — S.  M.,  five  months  old.  Taken  sick  on  November  nth,  and  death 
occurred  twenty-five  days  later.  Stools  were  greenish  with  much  mucus  but  no 
blood,  occasionally  watery,  one  to  five  a  day.  Temperature  touched  ioo°  F.  only 
once,  the  rest  of  the  time  it  was  990  F.  or  below. 

The  B.  dysentcrice  (Shiga)  was  found  two  weeks  before  death  at  the  first 
examination. 

Autopsy. — Small  intestine  normal  except  for  extreme  lower  end,  where  there 
is  slight  congestion.  Large  intestine — The  mucosa  is  congested  throughout,  the 
lower  part  extremely  so,  where  it  is  also  thickened. 

Microscopical. — Small  intestine  practically  normal.  Large  intestine — The 
lesions,  exclusive  of  edema  and  congestion  of  the  mucous  membrane,  are  insig- 
nificant. Slight  lymphoid  hypertrophy.  Spleen — There  is  a  moderate  endothelial 
hyperplasia  of  the  follicles. 

Bacteria  are  found,  chiefly  bacilli  negative  to  Gram,  in  the  superficial  part 
of  the  mucosa,  in  considerable  quantity. 

Case  III. — N.  D.,  ten  months  old.  Admitted  to  hospital  nine  days  before 
death,  with  diarrhea  and  with  a  temperature  of  970  F.  The  stools  were  one  to 
five  a  day,  yellow  and  brown,  with  mucus  and  only  once  a  little  blood.  He 
emaciated  rapidly  and  was  markedly  so  at  death. 

The  B.  dysentcrice  was  cultivated  from  the  mucous  membrane  of  the  colon 
at  autopsy. 

Autopsy. — Kidneys  degenerated.  Liver  soft.  The  other  organs  are  normal, 
except  the  colon,  the  mucous  membrane  of  which  is  very  much  congested  and 
the  submucosa,  on  section,  seems  to  be  thickened.  No  apparent  ulceration.  The 
mesenteric  glands  are  quite  enlarged,  but  only  slightly  congested. 


gtt  John  Hoivland. 

Microscopical. — Large  intestine — The  mucous  membrane  is  much  congested, 
though  there  are  no  hemorrhages.  The  lymphoid  follicles  are  a  little  swollen. 
The  submucosa  is  somewhat  thickened  from  edema  and  superficial  cellular  infil- 
tration, especially  about  the  blood  vessels.     The  muscular  layer  is  normal. 

Bacteria. — On  the  surface  of  the  mucosa  and  between  the  epithelial  cells  a 
moderate  number  of  organisms  negative  to  Gram  are  seen,  mostly  bacilli  of  the 
size  of  colon  bacilli,  arranged  in  small  clumps. 

Case  IV . — T.  W.,  five  months  old.  Was  admitted  to  the  hospital  suffering 
from  intestinal  indigestion.  During  the  first  month  he  improved  very  much  and 
gained  some  in  weight,  then  developed  a  diarrhea  and  began  to  lose  weight. 
A  day  or  two  afterward  the  first  trace  of  blood  appeared  in  the  stools,  only 
small  in  amount,  but  coincident  with  this  a  rise  in  temperature  from  990  F.  to 
103 °  F.,  and  this  remained  high,  sometimes  up  to  104'  F..  till  his  death, 
eight  days  later.  The  stools  toward  the  last  showed  no  blood  whatever, 
but  were  yellowish  green,  with  much  mucus,  and  there  was  also  considerable 
abdominal  rigidity  and  tympanites.  The  B.  dysenteries  was  obtained  by  culture 
from  scrapings  of  the  intestinal  mucosa. 

Autopsy. — Liver — Great  congestion,  with  fatty  infiltration.  Kidneys,  con- 
gested and  degenerated.  Spleen  congested.  Lungs — Hypostatic  pneumonia  in 
both. 

The  peritoneal  cavity  contains  cloudy  serum.  Between  the  loops  of  intestine 
there  are  some  delicate  bits  of  fibrin.  There  is  no  marked  injection  of  the 
vessels  and  the  peritoneum  has  lost  only  partially  its  normal  shining  appearance. 
Stomach  normal.  Small  intestine  appears  normal  except  for  slight  swelling  of 
Peyer's  patches  and  the  solitary  follicles.  Large  intestine  shows  extensive 
changes,  more  marked  at  the  lower  end.  The  wall  of  the  sigmoid  and  rectum  is 
very  much  thickened.  In  the  cecum  the  mucous  membrane  has  lost  is  normal 
smooth  appearance  and  is  dotted  over  with  granular  areas  and  marked  conges- 
tion. In  the  sigmoid  and  rectum  the  mucous  membrane  is  covered  with  a  grayish 
pseudo-membrane  that  strips  off  with  difficulty,  taking  with  it  all  structures 
down  to  the  very  much  thickened  submucosa.  The  mesenteric  glands  are  mod- 
erately swollen  and  congested. 

Microscopical. — Small  intestine — The  surface  epithelium  is  partially  denuded. 
The  mucous  membrane,  excepting  Peyer's  patches,  is  apparently  normal.  Peyer's 
patches  are  moderately  swollen,  there  being  a  hyperplasia  of  the  lymphoid  cells 
only.  There  is  no  necrosis  of  cells.  The  submucosa  and  muscularis  are  normal. 
Large  intestine — Sections  show  a  diffuse  necrosis  of  the  mucosa,  varying  in  in- 
tensity; in  some  places  only  the  superficial  edge  is  necrotic,  in  others  the  necrosis 
extends  through  the  entire  depth  and  as  far  as  the  muscularis  mucosa;.  All  the 
parts  of  the  mucosa  are  affected,  though  the  Lieberkuhnian  glands  suffer  espe- 
cially. The  blood  vessels  are  either  injected  or  closed  by  means  of  pink  thrombi. 
These  thrombi  show  little  or  no  fibrin  and  appear  to  be  made  up  of  coalesced 
red  blood  corpuscles.  The  surface  is  not  covered  with  a  definite  membrane, 
the  necrotic  tissue  adheres  to  the  subjacent  living  tissues  in  general,  occasionally 
it  is  lifted  up  and  gives  the  impression  of  being  a  pseudo-membrane.  At  the 
line  of  junction  of  the  living  and  dead  tissue  there  is  an  invasion  of  the  latter 
by  polymorphonuclear  cells  and  a  general  increase  of  the  cells  in  the  mucosa. 
Nuclear  fragmentation  is  not  abundant.  The  solitary  follicles  exhibit  a  somewhat 
mere  marked  hyperplasia  than  in  the  small  intestine,  the  centers  showing  endo- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  99 

thelial  proliferation.  The  mucosa  over  the  follicles  is  deficient.  The  submucosa 
is  edematous  and  contains  a  greatly  increased  number  of  mononuclear  cells, 
with  excentric  nuclei,  some  of  which  are  plasma  cells.  The  muscular  coat,  except 
for  the  fibrous  septa  which  show  an  increased  number  of  mononuclear  cells, 
is  normal.  There  is  a  massive  bacterial  development  in  the  necrotic  mucosa 
and  an  extension  of  bacteria  a  certain  distance  into  the  adjacent  living  mucosa. 
The  bacteria  consist  of  forms  staining  with  Gram  and  decolorizing  by  Gram; 
among  these  are  cocci  and  innumerable  bacilli.  The  invading  organisms  con- 
sist also  of  cocci  and  bacilli,  among  which  are  forms  having  the  colon-typhoid 
morphology.  Cultures  from  this  case  gave  colon  bacilli  from  the  peritoneum  and 
all  the  organs  while,  in  addition,  the  B.  dysenteries  was  obtained  from  the 
intestinal  contents. 

Case  V. — G.  C,  four  months  old.  Admitted  to  the  hospital  December  24th. 
Stools  yellowish  or  greenish,  two  a  day ;  no  temperature  till  January  23d,  then  a 
trace  of  blood,  with  gradual  rise  of  temperature  to  i02l/2°  F.  The  stools,  three 
to  nine  a  day,  contained  mucus  and  blood.  Death  five  days  later.  B.  dysenteries 
obtained  by  culture   from  the   scrapings  of  the  mucosa  of  the  colon. 

Autopsy. — Organs  practically  normal,  except  the  intestines.  Small  intestine — 
Follicles  in  the  ileum  prominent.  Large  intestine — In  the  cecum  and  ascending 
colon  a  number  of  solitary  follicles  are  seen,  slightly  elevated  above  the  mucous 
membrane.  The  mucous  membrane  is  moderately  congested  in  irregular  areas, 
but  otherwise  appears  quite  normal.  In  the  sigmoid  and  rectum  the  solitary 
follicles  are  distinctly  ulcerated,  showing  pock-marked  depressions,  and  the 
neighboring  mucous  membrane  is  congested.  The  mesenteric  glands  are  mod- 
erately  enlarged. 

Microscopical. — Large  intestine — The  general  mucous  membrane  is  normal, 
except  in  the  region  of  the  solitary  follicles,  which  are  moderately  enlarged  and 
over  which  the  mucosa  is  deficient.  There  is  no  marked  cellular  reaction, 
and  the  hyperlasia  of  the  follicles  is  a  lymphoid  one.  Other  coats  normal.  Small 
intestine — There  is  a  moderate  hyperplasia  of  the  follicles,  which  have  enlarged 
endothelial  centers.     The  submucosa  and  muscle  are  normal. 

Bacteria. — Only  a  few  bacilli  negative  to  Gram  are  found  on  the  surface  and 
of  those   positive   to    Gram   only   an   occasional   one. 

Case  VI. — C.  C,  two  years  old.  Had  never  been  out  of  the  institution. 
Three  weeks  before  death  he  was  discovered  to  be  suffering  from  an  acute 
nephritis ;  the  urine  contained  25  per  cent,  albumin,  blood  and  casts.  He  was 
very  edematous.  It  was  impossible  to  find  the  cause,  possibly  a  mild  scarlatina 
that  had  been  overlooked.  The  urinary  condition  did  not  change  nor  did  the 
edema.  He  had  green,  loose,  watery  stools  till  six  days  before  death,  then  he 
had  mucous  stools,  but  never  any  blood.  The  temperature  at  the  end  was  between 
ioo°  F.  and  1040  F. 

The  B.  dysenteries  was  isolated  three  days  ante-mortem. 

Autopsy. — The  lungs  are  edematous,  the  liver  fatty,  the  spleen  congested. 
There  is  ascites  and  anasarca.  The  kidneys  are  enlarged,  the  capsules  free, 
small  hemorrhages  are  seen  on  the  surface,  the  cortex  is  thickened  and  yellow- 
ish, the  pyramids  prominent,  the  consistency  soft.  Small  intestine — The  upper 
part  is  congested,  the  lower  150  centimeters  are  covered  with  a  thick,  almost  con- 
tinuous pseudo-membrane,  most  marked  toward  the  valve;  on  stripping  it  off, 
all  of  the  mucous  membrane  is  removed  with  it.     There  are  hemorrhages  beneath 


i  oo  John  Howland. 

this  membrane  which  ends  exactly  at  the  ileo-cecal  valve.  The  whole  wall 
of  the  intestine  is  very  much  thickened.  The  large  intestine  shows  a  few  small 
patches  of  congestion  and  the  follicles  are  enlarged.  The  mesenteric  glands  are 
enlarged  and  red. 

Microscopical.— The.  kidneys  show  a  marked  degeneration  of  the  epithelium; 
there  are  hemorrhages  into  the  tubules  which  contain  casts.  Within  the  cap- 
sules of  the  glomeruli  there  is  an  exudation  of  albumin  and  there  is  beginning 
exudation  into  the  kidney  stroma.  Ileum— The  mucous  membrane  is  almost 
completely  necrotic;  here  and  there  are  remains  of  imperfectly  preserved  crypts. 
The  necrotic  mucous  membrane  is  demarcated  from  the  submucosa  by  a  layer 
of  cellular  fragments,  by  hemorrhages  and  by  mononuclear  and  polymorpho- 
nuclear cells.  At  this  level  occasional  small  vessels  are  thrombosed.  The  sub- 
mucosa itself  is  swollen,  infiltrated  with  serum  and  fibrin,  and  shows  here  and 
there  preserved  and  fragmented  cells  similar  to  those  in  the  mucosa.  The  super- 
ficial muscular  layer  is  infiltrated  with  small  round  cells.  There  is  a  massive 
development  of  bacteria  in  the  necrotic  tissue  but  there  is  no  definite  false  mem- 
brane. In  the  colon  there  is  congestion  and  hyperplasia  of  the  follicles.  There 
are  scattered  areas  of  very  slight  superficial  necrosis,  no  ulceration,  and  between 
these  areas  the  intestine  is  fairly  normal. 

Bacteria. — The  surface  and  to  a  considerable  extent  the  whole  of  the  mucous 
membrane,  but  especially  the  remains  of  the  glands,  are  closely  packed  with 
bacilli  negative  to  Gram,  which  are  scattered  diffusely  throughout  and  also 
collected  in  large  masses. 

Case  VII. — J.  M.  The  child  was  two  years  old  and  an  imbecile.  She  was  taken 
sick  in  the  latter  part  of  November  with  diarrhea.  November  28th — No  Shiga 
bacilli  were  found,  but  they  were  present  on  December  1st.  She  had  diarrhea 
for  one  month  and  then  recovered  from  this  completely,  but  lost  ground  con- 
stantly and  developed  a  very  marked  broncho-pneumonia,  to  which  she  succumbed 
on  the  29th  of  January.  For  several  weeks  before  her  death  her  stools  had  been 
brown  and  normal,  and  examination  failed  to  show  the  presence  of  any  dysen- 
tery organisms. 

Autopsy. — There  is  a  very  marked  broncho-pneumonia,  with  beginning  ab- 
scess formation.  The  stomach  and  small  and  large  intestines  appear  normal 
but  for  congestion.  No  hemorrhages,  no  ulceration,  no  follicular  swelling,  and 
the  mucous  membrane  is  smooth  and  glistening. 

Microscopical. — Ileum — Slight  congestion.  No  ulceration,  no  necrosis,  mod- 
erate infiltration  of  the  interglandular  stroma,  with  mononuclear  cells,  practi- 
cally no  polynuclear.  This  infiltration  extends  down  to  the  submucosa,  which 
is  unaffected.  Colon — The  changes  are  the  same  as  in  the  ileum.  The  cellular 
infiltration  is  a  little  more  marked.  Almost  all  the  cells  lining  the  crypts  have 
been  transformed  into  "goblet"  cells.     The  solitary  follicles  are  unaffected. 

Bacteria. — Very  few  of  any  kind  are  found,  and  those  are  superficial  in  the 
extreme. 

Case  VIII. — G.  F.,  one  year  old.  Was  admitted  to  the  hospital  suffering 
from  diarrhea,  which  he  had  had  for  some  days.  Death  nineteen  days  later. 
Temperature  the  first  few  days  100-101°  F.,  rising  again  just  before  death. 
Stools,  two  to  five  a  day,  green  or  brown  and  watery,  with  flakes  of  mucus, 
never   any  blood. 

The  B.  dysenteric  found  two  weeks  before  death  and  again  at  autopsy. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  101 

Autopsy. — Lungs,  hypostatic  pneumonia.  Liver,  very  fatty.  The  follicles  of 
the  spleen  are  prominent.  Pancreas'  and  kidneys  negative.  Small  intestine — 
Minute  superficial  erosions  of  the  solitary  follicles  and  Peyer's  patches  are  seen. 
There  is  the  same  condition  of  the  follicles  in  the  colon.     No  ulceration. 

Microscopical. — Ileum — The  follicles  are  hyperplastic  and  there  is  very  super- 
ficial ulceration  over  them,  with  consequent  depressions.  Large  intestine — The 
general  mucosa,  except  in  the  neighborhood  of  the  follicles,  appears  normal.  The 
follicles  themselves  are  considerably  enlarged,  the  enlargement  being  due  chiefly 
to  an  increase  in  the  endothelial  elements  occurring  both  in  the  center  of  the 
follicles  and  in  the  periphery.  The  neighboring  mucosa  is  infiltrated  with  endo- 
thelial cells  and  there  is  a  central  depression  which  extends  into  the  follicle,  at 
which  point  the  epithelium  is  deficient.  The  submucosa  and  occasionally  just 
beneath  this  the  muscularis  show  a  distinct  cellular  infiltration,  the  cells  being 
of  the  mononuclear  variety.     The  muscle  is  normal. 

Bacteria. — Bacilli  negative  to  Gram  are  found  in  considerable  number,  extend- 
ing quite  deeply  in  apparently  healthy  tissue  toward  the  submucosa. 

Case  IX. — S.  T.,  one  year  old.  In  January  she  had  bronchitis.  Began  on 
February  ~th  with  broncho-pneumonia.  Five  days  later,  up  to  this  time  having 
been  constipated,  she  developed  diarrhea,  with  blood  and  mucus  in  the  stools, 
which  were  four  to  five  a  day.  The  temperature  was  falling  till  the  intestinal 
symptoms  developed,  then  it  rose  and  remained  continuously  high,  ioi°  F.  to 
1030  F.  till  death,  six  days  later.  Two  days  after  admission  the  stools  were 
examined  and  were  negative.  Five  days  before  death,  that  is  one  day  after  the 
diarrhea   developed,  the   examination   was  positive   for   Shiga  bacilli. 

Autopsy. — Lungs — Broncho-pneumonia.  All  other  organs  negative  but  the 
colon;  the  mucous  membrane  of  the  lower  two-thirds  of  this  is  much  thickened, 
appearing  edematous  and  congested. 

Microscopical. — The  mucous  membrane  of  the  colon  is,  in  general,  well  pre- 
served. There  is  a  transformation  of  many  of  the  cells  in  the  crypts  into  "gob- 
let" cells  and  some  of  these  crypts  are  dilated,  so  as  to  be  three  or  four  times 
as  large  in  diameter  as  the  normal  ones.  There  is  a  slight  general  congestion. 
The  follicles  are  moderately  enlarged,  due  to  a  proliferation  of  endothelial  cells. 
No  ulceration  and  no  infiltration  of  the  coats  with  cells.  The  submucosa  and 
the  muscularis   are  normal. 

Bacteria. — Organisms  positive  and  negative  to  Gram  infiltrate  the  mucous 
membrane  to  no  very  great  depth  and  in  small  numbers. 

Case  X. — R.  W.,  age  three  years.  Admitted  December  31st.  Death  Febru- 
ary 1st.  Diarrhea  constant,  stools  watery  and  foul  until  three  weeks  before 
death,  then  blood  and  mucus  were  noticed.  Temperature  occasionally  1010  F.  to 
1030    F.,    falling    shortly   to   normal. 

The  B.  dysenteries  was  isolated  three  weeks  and  again  two  weeks  before 
death. 

Autopsy. — Lungs — Marked  broncho-pneumonia.  Liver — Large  and  fatty. 
Stomach — Congested  throughout.  Small  intestine — Congested  and  follicles 
prominent  throughout.  Large  intestine — Markedly  congested,  with  rough,  granu- 
lar appearance  and  superficial  ulcerations. 

Microscopical.— Ileum — The  mucous  membrane  is  congested  and  the  lymphoid 
tissue  hyperplastic.  Large  intestine — The  mucous  membrane  is  in  places  greatly 
modified.    In  these  parts  the  granular  structures  are  invisible.    The  mucous  mem- 


102  John  Howland. 

brane  consists  of  small  cells  and  remains  of  crypts  which  are  much  compressed. 
On  the  surface  there  is  a  necrotic  pseudo-membrane  consisting  of  filaments  of 
fibrin  and  desquamating  necrotic  cells.  The  submucosa  and  muscularis  appear 
quite  normal.  An  additional  section  of  this  part  shows  in  addition  to  this 
pseudo-membrane  a  fair  number  of  polymorphonuclear  cells  and  cellular  frag- 
ments. 

Bacteria. — In  the  pseudo-membrane  there  are  many  organisms,  chiefly  cocci 
positive  and  bacilli  negative  to  Gram's  stain,  the  latter  predominating,  but  they 
do  not  invade  the  tissues  to  any  great  depth. 

Case  XL — H.  S.,  one  year  old.  Admitted  to  the  hospital  March  1st.  He  had 
been  in  the  hospital  a  month  before  suffering  from  diarrhea  and  anemia,  but 
had  been  discharged  in  good  condition.  His  temperature  on  admission  was 
102°  F.,  and  this  dropped  to  normal  for  one  day,  but  rose  again  irregularly  to 
1040  F.  and  remained  there  until  his  death,  six  days  later.  His  stools  were 
three  to  four  a  day,  green,  with  mucus  and  occasionally  blood.  There  were 
marked  meningeal   symptoms. 

The  B.  dysenteric  was  cultivated  from  the  stool  five  days  before  death. 

Autopsy. — Lungs  and  spleen  congested.  Liver  extremely  fatty.  Stomach 
normal.  Small  intestine — Peyer's  patches  and  the  solitary  follicles  are  a  little 
enlarged  and  present  a  "shaven  beard"  appearance.  Large  intestine — Congested, 
especially  at  the  lower  end,  and  the  follicles  are  prominent. 

Microscopical. — Small  intestine — The  ileum  is  in  an  excellent  state  of  preser- 
vation. Large  intestine — There  is  congestion  of  the  mucosa.  Almost  all  the 
epithelial  cells  of  the  crypts  are  "goblet"  cells.  The  lymphoid  tissue  of  the  solitary 
follicles  is  hyperplastic.  The  submucosa  and  muscularis  are  normal.  The  mesen- 
teric glands  are  congested. 

Bacteria. — Sections  stained  for  organisms  show  practically  none  positive  to 
Gram ;  negative  to  Gram  there  are  a  moderate  number,  superficially  situated,  and 
of  these  a  few  are  of  the  colon  size  and  form. 

Case  XII. — M.  M.,  ten  and  one-half  months.  Had  been  very  ill  for  one  month 
with  nasal  diphtheria,  double  otitis  and  cervical  adenitis.  Eight  days  before 
death  he  had  a  chill  and  a  rise  of  temperature,  followed  by  pulmonary  signs. 
The  temperature  went  up  to  1040  F.  and  remained  high  till  just  before  death, 
when  it  dropped  rapidly.  Seven  days  before  death  mucus  appeared  in  the  stools, 
but  there  never  was  any  blood.  A  culture  from  scrapings  of  the  mucosa  of  the 
colon  gave  a  growth  of  the  B.  dysenteries   (Shiga). 

Autopsy. — Lungs — Marked  pneumonia  of  the  right  lung,  with  empyema. 
Liver,  fatty.  Spleen,  large  and  soft.  Stomach,  post-mortem  digestion.  Small 
intestine,  negative.  Large  intestine,  no  ulceration,  no  congestion.  Mesenteric 
glands  enlarged. 

Microscopical. — Ileum  normal.  Colon — The  mucous  membrane  throughout 
is  practically  normal.  There  is  no  congestion  and  no  infiltration.  The  submucosa 
and  muscular  layers  are  normal.  The  follicles  are  intact  and  not  hyperplastic. 
Spleen — Very  marked  proliferation  of  the  endothelial  centers  of  the  Malpighian 
corpuscles. 

Bacteria. — Very  superficial  and  few  in  number. 

Case  XIII. — J.  W.,  two  months  old.  Was  admitted  to  the  hospital  March 
25th  with  pneumonia.  Died  April  3d.  He  had  one  to  three  yellow  and  green 
stools  a  day,  no  mucus  and  no  blood.     The  temperature  was  normal  throughout. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  103 

Five  days  before  death  no  Shiga  bacilli ;  two  days  before  death  the  bacilli  were 
isolated. 

Autopsy. — Lungs  typical  and  very  marked  broncho-pneumonia.  Spleen  large, 
dark  red  and  soft.  Liver  and  kidneys  degenerated.  Stomach  normal.  Small 
intestine— There  are  congested  Peyer's  patches  and  the  solitary  follicles  are  pig- 
mented and  present  a  typical  "shaven  beard"  appearance,  most  marked  low 
down.     Large  intestine  is  slightly  congested  and  the  follicles  prominent. 

Microscopical— Ileum — The  solitary  follicles  and  Peyer's  patches  are  a  little 
enlarged  from  an  increase  of  the  lymphoid  cells;  except  for  this  the  appearance 
is -normal.     Large  intestine— The  mucous  membrane  is  in  an  excellent  condition 
of  preservation.     The  follicles  are  slightly  swollen;  no  other  changes. 
Bacteria. — These  are  very  few  and  very  superficial. 

Case  XIV. — M.  T.,  eighteen  months  old.  An  enormously  rachitic  child,  with 
bronchitis  and  beginning  pneumonia.  Was  admitted  March  nth  and  died  March 
17th.  Constipated  most  of  the  time  till  two  days  before  death,  when  the  stools 
became  merely  mucus,  with  blood,  and  B.  dysenteric?  was  found. 

Autopsy. — Lungs — Beginning  broncho-pneumonia.  Small  intestine — Conges- 
tion in  the  lower  half  of  the  ileum,  with  the  solitary  follicles  and  Peyer's  patches 
slightly  enlarged.  Large  intestine — Intense  congestion  of  the  mucous  membrane 
of  the   entire  colon.      No   ulcers. 

Microscopical. — Small  intestine — The  agminated  follicles  are  much  swollen, 
the  centers  converted  into  large  germinal  centers  with  an  endothelioid  center 
and  in  the  periphery  the  endothelial  cells  are  also  increased.  The  mucosa  is  com- 
plete over  these  swollen  follicles.  The  submucosa  and  muscle  appear  normal. 
Large  intestine — In  all  of  the  crypts  are  numerous  "goblet"  cells.  Distinct 
hemorrhages  have  taken  place  into  the  mucosa.  In  the  neighborhood  of  one  of 
these  hemorrhages  there  is  an  area  of  necrosis  that  extends  to  the  submucosa. 
Where  this  occurs  the  staining  of  the  cells  is  absent  and  the  tissues  are  dis- 
integrated. A  large  number  of  bacteria  are  in  this  area,  but  no  reaction  is  pres- 
ent.    The   submucosa   is   intact. 

Bacteria,  both  positive  and  negative  to  Gram's  stain,  are  present  on  the 
surface,  but  in  the  necrotic  areas  they  are  found  in  countless  numbers. 

Case  XV. — A.  C.  Admitted  to  the  hospital  at  the  end  of  a  pneumonia,  with 
rales  the  only  signs  in  the  chest.  She  had  diarrhea,  stools  two  to  four  a  day, 
green  with  mucus.  Never  any  blood.  The  temperature  never  went  above  ioo°  F. 
Two  days  before  death  B.  dysenteric  (Shiga)   was  obtained  from  the  stools. 

Autopsy. — Liver  and  kidneys  degenerated.  Spleen  congested.  The  other 
organs,  including  the  stomach,  are  normal.  Small  intestine — The  solitary  fol- 
licles and  Peyer's  patches  are  a  little  swollen  and  appear  slightly  ulcerated;  the 
lower  two  inches  of  the  ileum  are  congested  and  changes  there  are  more  marked.' 
Large  intestine — All  the  follicles  are  prominent  and  many,  especially  in  the 
lower  portion,  are  dimpled.  The  whole  wall  in  the  lower  six  inches  is  much 
thickened  and  the  mucous  membrane  is  pale,  rough  and  granular  and  looks  ne- 
crotic.   The  mesenteric  glands  are  enlarged. 

Microscopical. — Small  intestine — There  is  denudation  of  the  surface  epi- 
thelium and  much  breaking  up  of  the  mucous  layer.  The  agminated  nodules 
are  swollen  ;  the  swelling  consists  in  a  moderate  lymphoid  hyperplasia  without 
necrosis.  The  general  mucous  membrane  is  normal  in  appearance.  The  sub- 
mucosa  is   moderately  infiltrated   with   mononuclear  cells,   of  which   some   show 


104  John  Howland. 

excentric  nuclei.  Large  intestine — The  mucous  membrane  is  thin,  with  a  great 
deficiency  in  the  crypts  of  Lieberkuhn.  The  solitary  nodules  are  prominent  but 
not  markedly  enlarged.  The  superficial  mucosa  in  many  places  refuses  to  stain 
and  in  others  the  staining  is  absent  or  poor  below  the  muscularis.  Fragments 
of  nuclei  are  occasionally  seen  in  the  non-staining  portion,  but  there  is  a  striking 
absence  of  leucocytic  reaction  in  the  adjacent  living  tissue.  The  mucosa  shows 
a  cellular  infiltration  similar  to,  but  more  intense  than,  that  in  the  small  intes- 
tine. The  spleen  is  congested  and  the  germinal  centers  of  the  Malpighian  bodies 
show  endothelial  hyperplasia. 

Bacteria. — When  stained  for  micro-organisms  a  moderate  number  of  Gram 
positive  bacteria  are  found.  The  Gram  negative  bacilli  of  colon  morphology 
extend  deeply  into  the  tissues.  The  necrotic  areas  are  closely  packed  with 
them  and  even  the  submucosa  contains  a  decided  number  in  its  more  superficial 
part,    especially    around   the    blood    vessels. 

Case  XVI. — R.  G.,  thirteen  weeks  old.  Admitted  at  five  weeks  old  for 
malnutrition.  Had  gonorrheal  ophthalmia  and  gonorrheal  joints.  Never  any 
mucus  or  blood  in  the  stools  and  always  a  subnormal  temperature.  Stools,  two 
to  six  a  day,  thin,  yellow  or  green.  B.  dysenteric?  was  found  two  weeks  before 
death. 

Autopsy. — Lungs — Beginning  broncho-pneumonia.  Stomach,  duodenum  and 
jejunum,  normal.  Ileum — Peyer's  patches  pigmented,  otherwise  not  affected. 
Large  intestine — The  upper  half  congested,  the  remainder  normal.  The  mesen- 
teric glands  not  enlarged.     Liver  congested.     Spleen  firm  and  hard. 

Microscopical. — Small  intestine — No  changes.  Large  intestine — There  is 
slight  congestion,  otherwise  all  the  coats   are  normal. 

Bacteria. — Very  few   of  any  kind  and  those   superficially  situated. 

Case  XVII. — J.  K.,  three  and  one-half  months  old.  Was  admitted  to  the 
hospital  suffering  from  malnutrition  and  indigestion.  Did  fairly  and  gained 
a  little  for  a  time.  Then  began  to  have  frequent  stools,  about  five  a  day,  that,  eight 
days  before  death,  contained  mucus,  never  any  blood.  The  temperature  for 
eight  days  of  the  disease  was  from  ioi°   F.  to  1030  F. 

The  B.  dysenteries   (Shiga)    was  found  eight  days  before  death. 

Autopsy. — Spleen — Congested  and  enlarged.  Lungs — Hypostatic  pneumonia. 
Stomach,  normal.  Small  intestine,  congested,  with  swelling  of  Peyer's  patches. 
Large  intestine,  intense  congestion  throughout ;  no  ulcerations  made  out ;  follicles 
swollen. 

Microscopical. — Ileum — Surface  columnar  epithelium  mostly  denuded.  The 
mucosa,  excepting  lymphoid  structures,  appears  normal.  The  agminated  nodules 
are  swollen  and  there  is  a  general  hj'perplasia  of  the  lymphoid  cells  and  a  marked 
proliferation  of  the  endothelial  cells  of  the  germinated  centers.  All  other 
structures  are  normal.  Large  intestine — The  changes  are  similar  to  those  in  the 
small    intestine ;    no    ulceration. 

Bacteria. — Very  few  of  any  kind  are  found. 

Case  XVIII. — A.  H.,  aged  seven  months.  Was  brought  to  the  hospital  with 
a  history  of  three  days'  diarrhea.  The  child  was  very  fat  but  very  rachitic.  She 
died  on  the  twelfth  day  of  the  disease.  The  stools  were  three  to  seven  a  day, 
green,  with  much  mucus,  never  any  blood.  The  temperature  was  irregular, 
990  to  1020  F.,  rising  just  before  death.     Was  given  10  c.c.  of  "Harris"  serum, 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  105 

with  temporary  improvement  but  no  lasting  benefit.  The  B.  dysenteries  was 
isolated  from  the  stools  ante-mortem. 

Autopsy. — Lungs — Lower  lobes  congested.  Liver  large  and  fatty.  Stomach, 
duodenum  and  jejunum  normal.  Ileum  congested  irregularly  in  the  lower 
eighteen  inches.  Large  intestine — Congested  in  patches  throughout  its  whole 
extent  and  has  partly  lost  its  smooth  appearance.  The  mesenteric  glands  are 
not  enlarged. 

Microscopical. — The  lymphoid  tissue  of  the  lower  ileum  and  colon  is  slightly 
hyperplastic.     Except  for  this  there  are  no  marked  histological  changes. 

Bacteria. — A  few  cocci  and  bacilli  are  found  in  the  superficial  mucosa. 

Case  XIX. — B.  F.,  aged  nine  months  twenty-seven  days.  Was  brought  to 
the  hospital  in  bad  condition,  with  diarrhea  and  without  any  accurate  previous 
history.  Was  very  emaciated,  had  meningeal  symptoms,  stiff  neck,  irregular 
pupils  and  internal  strabismus.  The  stools  most  of  the  time  were  yellow,  occa- 
sionally green,  with  a  trace  of  blood,  two  to  five  a  day.  The  temperature  at 
first  was  below  100°  F.,  rising  irregularly  to  1040  F.  just  before  death.  The 
duration  of  illness  in  the  hospital  was  fourteen  days.  B.  dysenteric  was  isolated 
three  days  before  death. 

Autopsy. — Lungs  edematous.  Liver  very  fatty.  Stomach  normal.  Small 
intestine — Upper  part  normal.  In  the  lower  two  feet  Peyer's  patches  are  en- 
larged, with  small  superficial  ulcerations  over  them.  Large  intestine — There  is 
congestion  most  marked  in  the  neighborhood  of  the  ileo-cecal  valve.  The  soli- 
tary follicles  are  dimpled.  The  changes  are  slight  in  the  descending  colon  and 
sigmoid.     The  mesenteric  glands  are  slightly  enlarged. 

Microscopical. — Small  intestine — The  general  mucosa  shows  little  alteration. 
As  the  confines  of  the  swollen  lymphoid  nodules  are  approached  the  villi  are 
swollen  and  rendered  more  obtuse  by  an  increase  of  the  lymphoid  cells.  The 
lymphoid  masses  are  markedly  enlarged,  the  new  cells  being  of  the  lymphoid 
habitus.  From  the  center  of  the  mass  there  is  a  funnel  shaped  depression  in 
which  the  lymphoid  cells  often  stain  poorly  and  over  which  the  mucosa  is 
imperfect.  The  submucosa  and  muscle  show  no  striking  alteration.  There  is 
no  striking  change  in  the  mucous  membrane  of  the  large  intestine,  but  the 
solitary  nodules  are  enlarged  in  a  manner  similar  to  that  described  in  the  small 
intestine  and  over  them  the  epithelial  layer  is   deficient. 

Bacteria  of  any  form  or  staining  properties  are  few  in  number. 

Case  XX. — R.  A.,  nine  months  twenty-six  days.  Was  brought  to  the  hos- 
pital in  poor  condition  with  Bednar's  aphthae.  He  had  stools,  three  to  six 
a  day,  very  foul,  green,  with  mucus,  occasionally  a  little  blood.  There  was  a 
moderate  temperature.  He  emaciated  gradually  and  died  marantic  after  two 
and  a   half  weeks   in  the   hospital. 

The  B.  dysenteric  was  obtained  by  scraping  the  mucous  membrane  at 
autopsy. 

Autopsy. — Lungs — Tubercles  scattered  throughout  both.  Bronchial  glands 
cheesy.  Liver  fatty.  Spleen  small  and  soft,  with  tubercles  on  surface  and  on 
section.  Stomach,  duodenum  and  jejunum  negative.  Ileum — Lower  foot  con- 
gested. In  the  lower  two  inches  the  Peyer's  patches  are  reddened  and  swollen. 
Large  intestine — Upper  one-eighth  of  colon  irregularly  congested.  Lower  seven- 
eighths,  much  congested  and  a  yellow  stringy  material  is  irregularly  distributed 


106  John  Howland. 

over  and  adherent  to  it.  Follicles  apparently  not  affected.  Mesenteric  glands 
slightly  swollen  and  reddened. 

Microscopical. — Large  intestine — The  mucosa  is  thickened,  the  thickening 
being  due  to  cellular  products  on  the  surface  of  the  mucosa.  These  cells  are 
desquamated  epithelium  and  other  surface  cellular  elements  which  cover  the 
crypts  to  a  considerable  depth.  The  crypts  themselves  are  of  quite  normal  ap- 
pearance. The  submucosa  and  muscle  are  normal.  The  solitary  follicles  are 
swollen,  but  not  markedly  so.  In  the  small  intestine  there  is  a  similar  desquama- 
tive condition  of  the  surface  cells  and  in  addition  a  moderate  enlargement  of  the 
agminated  follicles  due  to  an  increase  of  lymphoid  cells.  No  changes  in  the 
submucosa. 

Bacteria. — Bacilli  negative  to  Gram  are  found  in  the  superficial  portion 
of  the  mucosa  in  small  numbers  and  in  rather  greater  numbers  among  the 
desquamated  epithelial  cells. 

Case  XXI. — J.  S.,  seven  months  twenty-four  days  old.  A  well  nourished 
child;  began  to  be  ill  acutely,  with  temperature  1030  F.,  rising  in  twenty-four 
hours  to  104.5 °  F-  The  stools  at  first  were  brown  and  loose,  two  to  four  a  day. 
The  temperature  then  dropped  to  normal  and  after  three  days  the  stools  were 
normal  for  twenty-four  hours.  Following  this  a  rise  of  temperature  to  1030  F. 
and  the  stools  became  frequent  and  green,  with  mucus  and  blood.  Death  five  days 
later  despite  the  injection  of  10  c.c.  of  "Harris"  and  10  c.c.  of  "Seward"  serum. 
Temperature  for  the  last  three  days  100- 102 °  F.  Bacillus  dysenteries  was  iso- 
lated from  the  stools  five  days  before  death  and  was  also  found  post-mortem 
from  the  scrapings  of  the  mucous  membrane  of  the  colon. 

Autopsy. — Lungs — Slight  congestion  in  the  lower  lobes.  Liver  fatty.  Spleen 
small  and  firm.  Stomach  normal.  Small  intestine — Lower  six  inches  slightly 
congested.  Large  intestine — Congested  and  in  places  there  are  small  hemor- 
rhages into  the  mucosa.  The  mucous  membrane,  especially  near  the  ileo-cecal 
valve,  presents  very  small   superficial  yellowish   areas   of  apparent  necrosis. 

Microscopical. — Small  intestine  practically  normal.  Large  intestine — Through- 
out its  whole  extent  there  is  congestion.  In  the  sections  from  the  neighbor- 
hood of  the  ileo-cecal  valve  the  blood  vessels  of  the  mucosa  and  submucosa  are 
enormously  dilated ;  in  the  former  situation  there  are  actual  hemorrhages. 
There  are  small  areas  near  the  hemorrhages  whose  cells  stain  poorly  and  there 
is  actual,  although  superficial,  loss  of  substance.  There  is  considerable  inflamma- 
tory reaction  around  these  areas.  The  submucosa  is  much  infiltrated  with  mono- 
nuclear cells,  especially  in  the  superficial  portion.  The  muscularis  is  normal. 
In  other  parts  of  the   colon  the  changes  are  less  marked. 

Bacteria. — Cocci  and  bacilli,  positive  and  negative  to  Gram,  are  found  in 
great  numbers  in  the  neighborhood  of  the  necrotic  portions.  No  especial  type 
seems   to   predominate. 

Case  XXII. — M.  B.,  eleven  months  twenty-six  days  old.  While  in  the  institu- 
tion suffering  from  measles  she  had  had  a  diarrhea,  with  numerous  green  mucous 
stools,  no  blood.  The  B.  dysenteries  (Shiga)  was  then  isolated  from  the  stools. 
Two  weeks  later  she  developed  diphtheria  of  the  pharynx  and  larynx,  with  con- 
secutive broncho-pneumonia.  Death  one  week  after  the  first  signs  of  diph- 
theria. 

Autopsy. — Tonsils,  pharynx,  epiglottis,  larynx  and  vocal  cords  covered  by  a 
greenish-brown   false  membrane.     Lungs — Left   lower  lobe   is   consolidated  with 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  107 

hemorrhages  into  the  pleura.  Liver  very  fatty.  Spleen  large  and  soft.  Stomach, 
duodenum  and  jejunum  normal.  Ileum — Peyer's  patches  in  the  lower  portion 
are  reddened  and  covered  with  a  small  amount  of  adherent  yellowish  material. 
Remainder  normal.  Large  intestine — The  congested  mucous  membrane  is  thick- 
ened in  spots,  with  small  ulcerations.  The  follicles  show  superficial  erosions, 
especially  in  the  sigmoid. 

Microscopical. — Large  intestine — The  general  mucosa  appears  normal.  The 
follicles  are  enlarged,  the  hypertrophy  being  due  chiefly  to  lymphoid  cell  in- 
crease and  the  adjacent  submucosa  is  infiltrated  with  small  cells.  In  the  neigh- 
borhood of  the  follicles,  but  more  or  less  independent  of  them,  are  ulcers  of 
small  diameter  that  extend  often  to  the  submucous  coat.  Covering  these  ulcers 
and  the  adjacent  surface  of  the  mucosa  is  a  fibrinous  cellular  exudate  which  is 
closely  adherent.  The  submucosa  in  the  neighborhood  of  the  ulcers  and  even 
at  a  distance  shows  a  strong  mononuclear  infiltration.  The  other  coats  are 
normal.  Small  intestine — There  is  a  marked  hypertrophy  of  the  follicles,  with 
a  similar  fibrino-cellular  covering  upon  the  adjacent  mucous  membrane.  The 
general   submucosa  is   less   invaded  than   in  the  large  intestine. 

Bacteria  very  few   of  any  kind. 

Case  XXIII. — M.  K.,  five  months  twenty-two  days  old.  She  entered  the  hos- 
pital with  a  history  of  diarrhea  and  general  malnutrition.  She  was  in  the 
the  hospital  twelve  days.  Temperature,  99-1000  F.  Stools  four  to  five  a  day, 
green,  with  mucus.  Blood  first  appeared  one  week  before  death  and  on  the  last 
day  was  very  abundant.     The  B.  dysenteric  was  isolated  ten  days  before  death. 

Autopsy. — Lungs,  beginning  broncho-pneumonia.  Liver  fatty.  Spleen  small 
and  firm.  Stomach  normal.  Duodenum  and  jejunum  normal.  Ileum — .Small 
areas  of  congestion,  no  ulceration  or  involvement  of  the  lymphoid  tissue. .  Large 
intestine — Slight    irregular    congestion.      Few    prominent    follicles. 

Microscopical. — Except  for  a  moderate  congestion  there  are  no  histological 
changes  in  the  small  or  large  intestine. 

Bacteria  of  any  description  are  very  scanty. 

Case  XXIV. — H.  L.,  aged  one  year  four  months.  Brought  to  the  hospital 
with  signs  of  pneumonia  over  the  left  lower  lobe,  which  constantly  extended, 
and  a  temperature  of  1040  F.  Very  ill  from  the  start  and  had  five  to  eight  stools 
a  day,  green,  with  mucus,  but  no  blood.  Temperature  dropped  after  six  days 
to  990  F.,  but  rose  again  to  1020  F.  to  1030  F.,  and  remained  there  till  death, 
twenty-one  days  later.  B.  dyscntcrice  was  obtained  by  scraping  the  mucosa 
post-mortem. 

Autopsy. — Lungs — Broncho-pneumonia  scattered  in  both  lungs.  Bronchial 
glands  a  little  enlarged ;  no  signs  of  tubercle.  Liver  large,  soft  and  pale.  Spleen 
large  and  soft.  Kidneys  soft  and  pale.  Stomach,  duodenum  and  jejunum  nor- 
mal. Ileum — Peyer's  patches  swollen  and  congested.  Large  intestine  congested 
throughout,  with  some  loss  of  luster,  which  is  most  marked  low  down  and  in 
the  region  of  the  ileocecal  valve.  Follicles  not  prominent.  Mesenteric  glands 
much  enlarged  and  caseous,  tubercle  bacilli  demonstrated  by  staining.  No  other 
tuberculous  lesions  found. 

Microscopical. — Small  intestine — Congestion  and  moderate  hyperplasia  of  the 
agminated  follicles.  Large  intestine — The  mucous  membrane  in  general  is  nor- 
mal.    There  is  a  transformation  of  many  of  the  cells  in  the  crypts  into  "goblet" 


108  John  Howland. 

cells,  with  subsequent  dilatation  of  the  crypts  to  four  or  five  times  their  normal 
diameter.     The  other  coats  are  normal. 

Bacteria. — Very  few  of  any  kind  seen,  and  these  are  very  superficial. 

Case  XXV. — C.  B.,  eight  months  twenty-two  days  old.  A  poorly  nourished 
child,  with  indefinite  signs  in  his  chest,  was  admitted  to  the  hospital  with  diar- 
rhea, which  persisted  till  death,  twenty-eight  days  later.  The  stools,  four  or 
five  a  day,  were  green  and  yellow,  with  mucus,  occasionally  a  trace  of  blood. 
Temperature,  98°-ioo°  F.  Emaciated  rapidly.  B.  dysenteries  was  isolated  seven 
days  before   death. 

Autopsy. — Lungs — There  are  fresh  tubercles  on  the  visceral  pleura,  but  the 
parietal  pleura  is  normal.  The  left  apex  contains  numerous  caseous  tuberculous 
masses,  together  with  small  fresh  tubercles.  The  bronchial  glands  are  enlarged 
and  cheesy.  Liver  fatty.  In  the  spleen  are  small  fresh  tubercles.  Stomach 
normal.  Duodenum  and  jejunum  normal.  Ileum — The  Peyer's  patches  are 
enlarged  and  ulcerated,  the  edges  of  the  ulcers  thickened  and  they  extend  deeply 
into  the  muscular  coat.  They  are  round,  not  longitudinal  or  perpendicular  to 
the  long  axis  of  the  gut.  While  their  general  appearance  is  tuberculous  no 
tubercles  are  seen  on  the  peritoneal  coat.  Large  intestine — All  the  solitary 
follicles  appear  enlarged  and  the  edges  of  many  are  congested.  The  majority 
are  slightly  pitted.     The  mesenteric  glands  are  enlarged  and  caseous. 

Microscopical. — There  are  tuberculous  processes  in  both  the  small  and  large 
intestine,  which  so  obscure  the  other  lesions  that  it  is  not  considered  advisable 
to  draw  any  conclusions  from  this  cafe. 

Case  XXVI. — V.  M.,  six  months  nineteen  days  old.  A  poorly  nourished 
child;,  was  admitted  to  the  hospital  with  a  history  of  several  days'  diarrhea. 
He  was  under  observation  five  weeks,  with  practically  a  normal  temperature, 
rising  occasionally  to.1020  F.  The  stools  were  fluid  and  green,  two  to  five  a 
day,  no  blood,  but  slight  amount  of  mucus.  B.  dysenteric  was  isolated  from  the 
stools   on  the   day   of  admission. 

Autopsy. — Liver  large  and  soft.  Spleen  hard  and  small.  Small  intestine — 
Peyer's  patches  congested ;  no  ulceration.  Large  intestine — The  mucous  mem- 
brane near  the  ileo-cecal  valve  is  congested;  throughout  the  rest  of  the  colon 
the   follicles  are  pigmented  and  slightly  depressed. 

Microscopical. — Owing  to  the  length  of  time  of  the  autopsy  after  death,  post- 
mortem changes  had  taken  place  in  the  intestines  that  made  them  unsuitable  for 
microscopical    examination. 

Case  XXVII. — C.  C,  seven  months.  There  was  a  history  of  two  days' 
diarrhea  before  admission  to  the  hospital.  The  stools  were  green  with  mucus, 
two  to  six  a  day.  No  blood  till  two  days  before  death,  after  an  illness  of  thirty- 
four  days.  Temperature  980  F.  to  1010  F.,  until  just  before  death,  then  a  rapid 
rise  to  1040  F.,  followed  by  a  fall.  The  Shiga  bacillus  was  not  found  twenty- 
eight  days  before  death ;  an  examination  for  it  was  positive  eighteen  days  before 
death. 

Autopsy. — Liver  fatty.  Spleen  firm  and  dark.  Stomach  normal.  The  small 
intestine  appears  normal  except  the  last  two  inches  of  the  ileum,  which  are  greatly 
congested.  One  small  spot  the  size  of  a  pea  is  thickened,  exfoliating  and  cov- 
ered with  a  necrotic  mass.  The  large  intestine  is  very  much  thickened  through- 
out its  whole  extent,  apparently  due  to  a  swelling  of  the  submucosa.  There  is 
congestion  throughout      In  places  extending  for  two  to  three  inches  there  are 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  109 

hemorrhages  into  the  mucosa.  In  no  place  does  the  mucous  membrane  appear 
smooth.  No  ulceration  is  made  out,  no  follicular  enlargement.  The  mesenteric 
glands   are  a  little  enlarged. 

Microscopical. — The  lower  ileum  at  one  point  is  greatly  modified.  The  struc- 
ture of  the  mucosa  is  almost  obliterated  on  account  of  great  swelling  of  the 
villi  and  the  greatly  diminished  staining  power  of  the  cells.  In  places,  how- 
ever, the  crypts  are  fairly  preserved.  There  is  much  congestion  and  definite 
hemorrhage  into  the  tissues.  Overlying  the  mucosa  and  attached  to  it  in  a 
definite  locality  is  a  necrotic  pseudo-membranous  mass  containing  fibrin  and 
desquamated  and  emigrated  cells.  The  muscularis  mucosae  is  preserved  prac- 
tically intact  but  the  submucosa  is  swollen,  infiltrated  with  serum  and  mono- 
nuclear cells,  the  blood  vessels  being  injected.  The  muscular  coat  appears  normal 
as  does  the  peritoneum.  Colon — The  mucosa  is  fairly  normal,  although  there 
are  hemorrhages  into  it,  at  which  points  the  staining  of  the  cells  is  very  im- 
perfect. The  hemorrhages  extend  into  the  submucosa,  which  is  swollen,  con- 
taining an  excess  of  mononuclear  cells,  though  it  is  much  less  affected  than  the 
submucosa   of  the   small   intestine   described. 

Bacteria. — There  is  a  massive  bacterial  growth  in  the  pseudo-membranous 
mass  as  well  as  in  the  mucosa  of  the  lower  ileum  and  colon.  Organisms,  cocci 
and  bacilli  are  found  in  great  numbers,  but  the  bacilli  of  the  colon  habitus  and 
staining  qualities  predominate,  especially  in  the  mucous  membrane,  where  they 
extend  as  far  as  the  muscularis  mucosae  but  no  deeper. 

Case  XXVIII. — M.  H.,  eight  months  old.  Ill  ten  days  with  diarrhea.  Stools 
one  to  seven  a  day,  green  and  fluid,  with  mucus ;  no  blood.  Temperature,  980- 
IC2°  F.,  only  reaching  this  latter  figure  once.  She  lost  flesh  rapidly  and  died 
marantic.  B.  dysenteries  (Shiga)  was  isolated  from  the  stools  three  days  before 
death. 

Autopsy. — Liver  fatty.  Spleen,  small,  soft,  atrophic.  Stomach  negative. 
Small  intestine  negative  except  for  "shaven  beard"  appearance.  Large  intes- 
tine— Follicles  a  little  prominent  and  pigmented.  No  ulceration.  Mesenteric 
glands  not  enlarged. 

Microscopical. — Ileum  and  colon  present  no   marked  histological  changes. 

Bacteria  practically  absent. 

Case  XXIX. — L.  U.,  eight  months  eight  days  old.  A  very  poorly  nourished 
child,  was  admitted  to  the  hospital  in  a  moribund  condition,  with  a  normal  tem- 
perature, but  with  frequent  green  fluid  stools,  containing  mucus  and  blood. 
Death  two  days  later.  Temperature  1040  F.  at  death.  The  B.  dysenteries  was 
isolated  the  day  before  death. 

Autopsy. — Liver  very  fatty.  Spleen  atrophic.  Stomach,  duodenum  and 
jejunum  normal.  Ileum — The  Peyer's  patches  are  pigmented;  otherwise  normal. 
Large  intestine — The  mucous  membrane  appears  normal.  A  few  follicles  near 
the  ileocecal  valve  are  prominent. 

Microscopical. — The  mucous  membrane  of  the  ileum  and  colon,  as,  in  fact, 
all  the  coats,  are  quite  normal.  In  the  colon  there  is  slight  hyperplasia  of  the 
lymphatic  tissue. 

Bacteria. — There  are  very  few  organisms  of  any  kind  discernible  and  these 
are  most  superficial. 

Case  XXX. — M.  W.,  four  months  six  days  old.  A  fairly  nourished  child,  with 
a  history  of  four  days'  diarrhea ;    was  admitted  to  the  hospital  in  a  condition  of 


no  John  Howland. 

extreme  prostration.  The  stools  were  frequent  and  green,  with  a  slight  amount 
of  mucus  and,  just  ante-mortem,  a  trace  of  blood.  She  had  a  very  slight  tem- 
perature, varying  from  o,8°-ioo°  F.  She  took  nourishment  poorly  and  vomited 
what  she  did  take.  Death  three  dajs  later.  The  B.  dysenteries  (Shiga)  was 
obtained  by  scraping  the  intestinal  mucosa  pest-mortem. 

Autopsy. — Liver  soft  and  fatty.  Spleen  normal.  Stomach,  duodenum,  jejunum 
and  ileum  normal.  Large  intestine — Congestion  throughout,  but  more  intense 
in  the  cecum  and  sigmoid.     No  ulcerations.     Follicles  are  not  affected. 

Microscopical. — Ileum  normal.  Large  intestine — The  mucosa  is  congested, 
the  blood  vessels  widely  dilated  with  blood,  but  there  are  no  hemorrhages,  and 
except   for  this,   quite  a  normal   histological   appearance. 

Case  XXXI. — J.  R.,  fifteen  months  old.  Had  suffered  for  months  previous 
from  malnutrition  and  vomiting.  Admitted  at  the  age  of  ten  months.  Weight 
seven  pounds  and  fifteen  ounces.  Improved  slowly  and  one  month  later  was  tak- 
ing food  well  and  gaining  in  weight.  Then  vomiting  occurred  and  he  lost  weight 
though  the  stools  were  normal.  Three  months  after  admission  the  stools  became 
loose,  four  to  six  a  day,  no  blood,  but  later  a  little  mucus  and  undigested  food. 
This  condition  persisted  for. a  long  time,  and  twenty-nine  days  after  the  beginning 
of  the  diarrhea  the  B.  dysenteric?  (Shiga)  was  obtained  from  the  stools.  Two 
days  later  the  bacillus  was  not  found  and  at  the  autopsy  three  weeks  later  it 
could  not  be  recovered  by  scraping  the  mucous  membrane  of  the  colon.  The 
child  emaciated  constantly  and  died  in  a  condition  of  extreme  marasmus,  weigh- 
ing but  six  pounds  four  ounces. 

Autopsy. — Lungs  congested.  Liver  small  and  dark.  Spleen  dark  red,  fol- 
licles prominent.  Stomach  and  duodenum  normal.  Jejunum  contained  two 
small  ulcers.  Ileum — Peyer's  patches  are  slightly  swollen  and  a  few  small 
ulcers  are  present  in  them.  Colon — Here  are  many  ulcers  extending  through 
the  mucosa  and  even  down  to  the  muscular  coat,  but  the  peritoneal  surface  is 
everywhere  quite  smooth.  The  ulcers  are  irregularly  oval  or  round,  with  raised 
edges,  and  are  not  limited  to  the  solitary  follicles,  which  are  not  enlarged. 

Microscopical. — Small  intestine — The  ulcers  are  relatively  superficial  and  in- 
volve the  layer  of  the  crypts,  but  do  not  extend  through  the  mucosa.  The  base 
consists  of  granulation  tissue  diffusely  spread  out,  extending  beyond  the  limits 
of  the  ulcer  and  invading  the  adjacent  mucous  membrane,  the  crypts  of  which 
are  widely  separated,  and  also  invading  at  a  distance  the  submucosa.  The 
muscular  coat  escapes.  Large  intestine — The  chief  lesion  is  an  ulcerative  one, 
affecting  the  mucous  membrane  and  to  a  marked  extent  the  submucosa.  The 
ulcer  is  clear,  the  base  of  it  consisting  of  granulation  tissue  in  a  state  of  ad- 
vanced formation.  The  superficial  edge  of  the  ulcers  presents  a  reticulated  ap- 
pearance due  to  a  superficial  necrosis  of  the  granulation  tissue  in  which  are  fibrin 
and  degenerated  mononuclear  cells.  Where  the  glands  are  retained  many  have 
become  dilated  so  as  to  form  small  cysts.  The  spleen  is  interesting  in  showing 
a  marked  endothelial  transformation  of  the  germinal  centers  of  the  Malpighian 
bodies. 

Bacteria. — A  very  few  cocci  and  bacilli  are  found  on  the  surface  of  the  ulcers 
as  well  as  in  the  mucous  membrane. 

Case  XXXII. — R.  M.,  five  months  old.  Was  nursed  for  one  month  and  after 
that  fed  on  diluted  cow's  milk.  For  eight  days  she  suffered  from  vomiting  and 
diarrhea.     There  was   a   slight   irregular  temperature.     In  the   hospital  six  days 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  in 

with  constant  diarrhea,  stools  green  or  yellowish  and  watery,  occasionally  mucus, 
no  blood.  Died  very  poorly  nourished.  The  B.  dysenteries  was  isolated  from 
the  stools  five  days  before  death  and  again  at  autopsy,  from  scrapings  from  the 
colon. 

Autopsy. — Liver  moderately  fatty.  Spleen  small,  dark  arid  firm.  Stomach 
normal.  Small  intestine — Many  small  ulcers  extending  through  the  mucosa 
only  and  not  limited  to  the  solitary  follicles.  These  are  present  in  the  duo- 
denum, jejunum  and  ileum.  Almost  all  the  Peyer's  patches  are  swollen  and 
contain  several  small  ulcers.  No  deep  ones.  Large  intestine — The  solitary  fol- 
licles are  a  little  enlarged,  no  ulceration.  Mesenteric  glands,  slightly  swollen  and 
gray. 

Microscopical — The  small  intestine  shows  a  general  hyperplasia  of  Peyer's 
patches,  the  enlargement  being  due  partly  to  an  increase  of  lymphoid  cells  and 
partly  to  endothelial  transformation  of  the  germinal  centers.  The  mucosa 
in  the  neighborhood  of  these  large  follicles  shows  an  increase  in  lymphoid  cells. 
The  ulcer  examined  microscopically  within  a  Peyer's  patch  extends  about  half 
way  through  the  mucous  membrane  though  the  cells  of  the  patch  are  degen- 
erated throughout.  The  surface  of  the  ulcer  is  covered  by  a  fibrinous  and 
cellular  exudate  and  the  vessels  within  that  portion  of  the  mucosa  are  throm- 
bosed. The  submucosa  shows  an  infiltration  of  the  lymphoid  cell  type.  Large 
intestine. — There  is  a  "goblet"  cell  transformation  of  the  epithelium.  The  spleen 
presents  an  endothelioid  transformation  of  the  germinal  centers. 

Bacteria. — Only  a  few  and  those  superficially  situated. 


From  a  study  of  these  tabulated  cases  it  seems  that  they  fall  with 
considerable  accuracy  into  several  different  groups  according  to  the 
histological  findings.  Group  A,  comprising  cases  4,  6,  10,  22  and  27, 
represents  the  most  severe  changes  met  with,  which  are  more  like 
those  found  by  Flexner  and  Strong  in  the  adult  dysenteries  of  Manila 
than  any  I  have  to  report.  In  these  cases  the  change  is  a  pseudo- 
membranous one,  though  the  membrane  is  bv  no  means  continuous, 
but  of  irregular  distribution  in  cases  10,  22  and  27;  in  cases  4  and  6, 
however,  it  is  very  extensive — in  4  in  the  colon  and  in  6  in  the  ileum. 
This  pseudo-membrane  is  composed  chiefly  of  necrotic  tissue,  desqua- 
mated cells  and  countless  bacteria.  Fibrin  plays  a  very  small  part  in  it 
— two  of  the  cases,  and  those  the  most  intense,  4  and  6,  showing  none 
at  all.  There  is  necrosis  of  the  mucosa  in  all  these  cases,  and  it  is 
this  chiefly  which  gives  the  appearance  of  a  false  membrane,  but  the 
necrosis  does  not  extend  beyond  this  coat.  In  this  necrotic  tissue  and 
at  its  border  there  are  hemorrhages  and  thromboses,  and  it  is  divided 
from  the  healthy  tissue  by  a  zone  of  mono-  and  polynuclear  cell  infil- 
tration. 

The  submucosa  in  four  of  the  cases  of  this  group  is  much  affected, 
it   is   swollen   both   from   edema   and   from   cellular   infiltration.      This 


ii2  John  Howland. 

infiltration  is  composed  of  mononuclear  cells,  many  with  the  excentric 
nuclei,  characteristic  of  plasma  cells,  and  is  found  most  marked  about 
the  blood  vessels.  The  submucosa  in  the  fifth  case  is  unaffected.  The 
muscular  coat  is  spared  except  for  a  slight  mononuclear  infiltration 
along  the  fibrous  septa  in  one  case  and  the  peritoneal  coat  is  normal 
save  in  the  case  of  peritonitis. 

It  is  interesting  to  note  in  this  connection  that  though  such  cases 
in  adults  run,  as  a  rule,  very  acute  courses  one  of  these  children  lived 
eighteen  and  two,  twenty-one  days  after  the  bacillus  was  isolated  from 
the  stools,  while  the  other  children  survived  only  six  and  eight  days 
after  the  stools  contained  mucus  or  blood. 

Two  cases,  6  and  22,  were  so-called  "terminal  infections,"  occurring 
in  nephritis  and  measles,  respectively,  the  latter  being  also  complicated 
by  diphtheria. 

In  Group  B,  comprising  cases  1,  5,  8  and  19,  we  find  a  different 
picture.  Here  the  mucous  membrane  in  both  small  and  large  intestines 
is,  in  general,  in  a  good  state  of  preservation ;  it  is  the  lymphoid  ele- 
ments that  suffer.  In  three  cases  both  small  and  large  intestines  were 
involved  in  the  process,  in  the  fourth  only  the  colon.  The  change  con- 
sists in  a  hyperplasia  of  the  lymph  follicles,  both  agminated  and  soli- 
tary, and  this  hyperplasia  is  lymphoid  in  three  of  the  cases  and  endo- 
thelioid  in  the  fourth.  The  elements  of  these  follicles  show  a  tendency 
to  invade  the  surrounding  tissue.  Over  these  follicles  there  is  a  defi- 
ciency of  the  epithelium  and  more  or  less  excavation  of  the  follicles 
themselves,  causing  the  well-known  "pitting." 

The  submucosa  was  in  all  cases  approximately  normal  nor  did  the 
muscular  or  peritoneal  coats  show  any  change. 

The  case  of  Park  and  Carey/"  the  only  autopsy  in  an  infant  suffering 
from  undoubted  Shiga  infection  that  I  have  been  able  to  find  reported 
up  to  this  time,  evidently  belongs  to  this  group,  the  lesions  being 
chiefly  in  the  solitary  follicles. 

Of  this  group  three  of  the  infants  were  known  to  have  been  ill  for 
fourteen  days  or  over,  and  the  fourth  had  diarrhea  for  only  five  days, 
but  before  this  his  stools  were  green  and  rather  numerous  and  had 
not  been  examined,  so  that  it  is  possible  that  the  bacillus  was  present 
for  a  longer  time.  These  changes  are  what  one  would  expect  in  sub- 
acute cases  with  a  more  delayed  termination,  and,  as  mentioned  above, 
this  is  true  of  three  of  the  cases  at  least  and  possibly  of  the  fourth. 
Case  1  was  a  terminal  infection  secondary  to  a  broncho-pneumonia ; 
the  other  three  were  primary  cases. 

Group  C  includes  those  cases  characterized  by  superficial  necrosis 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  113 

and  ulceration  in  the  mucous  membrane,  not  limited  to  the  follicles, 
as  in  Group  B,  and  not  accompanied  by  the  formation  of  a  pseudo- 
membrane  as  in  Group  A.  Of  this  group  there  are  five  examples,  viz., 
14,  15,  20,  21,  32. 

The  changes  here  consist  in  congestion  and  hemorrhage  into  the 
mucosa,  with  necrosis  of  isolated  portions  of  the  mucous  membrane, 
which  necrotic  portion  may  be  exfoliated  so  as  to  form  ulcerations  on 
the  surface.  The  necrotic  area  and  ulcerations  are  usually  surrounded 
by  a  zone  of  inflammatory  reaction.  The  lymphatic  tissue  shows  more 
or  less  participation  in  the  process.  The  submucosa  escapes,  with  the 
exception  of  the  one  case  where  there  is  a  cellular  infiltration.  The 
other  coats  are  unaffected. 

Two  of  these  cases  were  very  acute,  lasting  but  two  and  eight  days, 
respectively,  while  each  of  the  others  ran  a  course  of  about  two  weeks. 

Cases  14  and  15  were  terminal  infections  secondary  to  pneumonia. 

The  Group  D,  embracing  those  cases  that  show  microscopically  but 
few  discoverable  lesions,  is  a  large  one,  including  cases  2,  3.  9,  11,  12, 
13,  16,  17,  18,  23,  24,  28,  29  and  30.  Several  facts  may  contribute  to 
account  for  this.  I  have  not  considered  the  loss  of  the  superficial  epi- 
thelium as  a  pathological  lesion  and  have  regarded  only  loss  of  sub- 
stance as  true  and  not  an  artifact  when  it  has  been  surrounded  by  a 
definite  reactionary  zone.  The  autopsies  in  most  of  the  cases,  un- 
fortunately, could  not  be  obtained  immediately  after  death,  as  they 
should  be,  to  draw  any  definite  conclusions  from  the  condition  of  the 
superficial  epithelium.  Loss  of  substance  occurs  so  easily  that  in  order 
to  avoid  false  conclusions  the  above  outlined  plan  was  adopted.  It  is 
possible  that  autopsies  obtained  a  few  minutes  after  death  will  allow 
of  some  positive  deductions  in  regard  to  the  epithelial  coating.  Then . 
too,  the  microscope  fails  to  help  us  very  much  in  the  vascular  changes 
in  the  mucosa  on  account  of  the  various  processes  to  which  the  tissue 
has  to  be  subjected  in  the  course  of  hardening,  and  for  this  reason  the 
macroscopic  examination  probably  gives  us  a  truer  conception  of  the 
amount  of  congestion.  And,  lastly,  five  cases  of  this  group  were  ter- 
minal infections  occurring  in  children  suffering  from  serious  and  even 
fatal  diseases,  and  others  were  in  badly  nourished  institutional  in- 
fants, to  whose  marasmus  the  infection  with  the  Shiga  bacillus  was 
terminal.  The  infection  was  of  a  comparatively  short  duration  and 
their  reaction  undoubtedly  poor.  Beyond  congestion,  moderate  hyper- 
plasia of  the  lymphoid  tissue  and  in  one  case  a  little  cellular  infiltra- 
tion of  the  superficial  portion  of  the  submucosa,  there  was  very  slight 
histological  change. 


ii4  John  Howland. 

Case  31  presents  lesions  quite  distinct  from  any  of  the  others.  The 
ulcerations  were  very  deep  and  were  in  the  process  of  repair,  death 
being  due  to  marasmus  after  all  intestinal  symptoms  had  ceased  and 
the  Shiga  bacillus  had  disappeared  from  the  stools,  nor  could  it  be 
found  post-mortem  by  scraping  the  mucosa. 

Cases  25  and  26  could  not  be  included  in  any  of  the  groups  owing 
to  their  unsatisfactory  microscopical  examinations,  while  case  7  is 
worthy  of  special  mention,  though  presenting  practically  no  abnormal 
change,  on  account  of  the  fact  that  the  child  had  recovered  completely 
from  the  original  infection  only  to  fall  a  victim  later  to  pneumonia. 

From  the  foregoing  it  will  be  noticed  that  the  severe  cases  are  de- 
cidedly in  the  minority.  The  lesions  occur  with  the  greatest  frequency 
in  the  mucosa  of  the  colon  and  the  lower  few  inches  of  the  ileum,  those 
in  the  colon  being  usually  much  more  intense  and  extensive.  The 
pseudo-membrane  in  case  6,  however,  is  confined  entirely  to  the  small 
intestine,  the  ulcerations  in  case  32  are  confined  entirely  to  the  small 
intestine,  and  case  27,  although  only  a  little  of  the  ileum  was  affected, 
showed  its  most  intense  process  there.  Though  the  submucosa  is  at 
times  affected  there  is  no  considerable  change  unless  the  mucosa  has 
suffered  severely.  Only  in  the  most  intense  inflammations  does  the 
muscular  coat  show  participation  in  the  process,  and  then  very  slightly, 
while  the  peritoneum  escapes — case  4,  with  general  peritonitis,  being 
an  exception. 

As  far  as  the  other  organs  are  concerned  there  were  no  character- 
istic findings.  The  mesenteric  glands  are  usually  somewhat  enlarged, 
rarely  markedly  so,  and  grayish  or  pinkish.  The  lungs  show  hypo- 
static congestion  and  small  areas  of  broncho-pneumonia  unless  the 
Shiga  infection  is  secondary  to  some  more  pronounced  pulmonary  lesion. 
The  liver  is  fatty  in  about  the  same  percentage  as  in  other  infantile 
conditions.  The  spleen  is,  as  a  rule,  unaffected,  but  when  some  other 
infection  is  added  presents  the  characteristics  common  in  all  infectious 
diseases.    The  kidneys  show,  as  a  rule,  cloudy  swelling. 

In  eight  cases  cultures  were  made  from  all  the  organs  at  autopsy 
but  never  was  the  bacillus  found  except  in  the  intestinal  tract.  The 
culture  tubes — when  tissues  from  the  organs  were  transplanted  in  small 
quantity,  except  the  lungs,  where  many  different  organisms  were  found, 
— either  remained  sterile  or  showed  a  growth  of  colon  bacilli.  In  one 
case,  streptococci  were  found  in  the  liver.  This  negative  bacterio- 
logical finding  is  the  characteristic  one  in  adults,  though  general  blood 
infections  have  been  reported.  The  method  advised  by  Flexner,  of 
plating  considerable  quantities  of  tissue,  by  which  he  was  able  to  de- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  115 

monstrate  the  presence  of  bacilli  in  the  liver  and  mesenteric  glands,  was 
not  employed. 

An  examination  for  micro-organisms  gives  no  very  definite  results. 
An  innumerable  host  of  bacteria,  cocci  and  bacilli,  are  present  in  the 
pseudo-membrane  and  in  the  necrotic  tissues;  in  the  center  of  these 
masses  they  are  about  equally  distributed,  but  one  receives  the  im- 
pression that,  in  the  tissues  surrounding,  the  bacilli  of  the  colon-typhoid 
morphology  and  staining  properties  predominate,  but  it  is,  of  course, 
impossible  to  say  that  these  are  all  Shiga  bacilli.  In  the  milder  grades 
of  inflammation  the  organisms  of  any  kind  are  few  in  number,  very 
superficially  situated,  with  no  particular  type  predominating.  In  this 
series  the  organisms  invaded  the  submucosa  in  case  1 5  only. 

In  examining  for  bacteria  in  the  sections  my  findings  agree  more 
nearly  with  those  of  Flexner,3  who  found  in  adults  a  general  admixture 
of  organisms  on  the  surface  of  and  in  the  mucosa,  with  a  submucosa  un- 
invaded,  rather  than  with  those  of  Strong  and  Musgrave,  who  found 
organisms  not  only  in  the  mucosa  but  all  through  the  areolar  tissue, 
muscularis  mucosas  and  submucosa  down  to  the  muscular  coat. 

It  is  interesting  at  this  time  to  compare-  somewhat  in  detail  the 
pathological  findings  in  these  cases  with  those  observed  by  Flexner,3 
and  by  Strong  and  Musgrave,  in  Manila,4  the  specific  germ  being  the 
same.  When  we  do  this  we  find  that  only  one  of  these  groups  (A) 
is  comparable  in  any  way  with  their  Manila  cases,  though  this  bears 
many  striking  resemblances.  There  is  a  pseudo-membrane  composed 
of  necrotic  tissue,  emigrated  and  desquamated  cells  and  myriads  of 
bacteria.  Flexner  lays  great  stress  on  the  fibrin  in  this  pseudo-mem- 
brane, while  Strong  and  Musgrave  do  not  mention  its  presence.  A 
moderate  amount  of  fibrin  was  found  in  some,  not  all,  of  my  cases. 
The  submucosa  is  much  affected,  according  to  these  observers,  and 
this  was  my  observation,  and  the  changes  were  the  same ;  but  Flexner 
speaks  of  much  fibrin  formation  in  this  coat  as  well  as  hemorrhages, 
the  former  of  which  Strong  and  Musgrave  do  not  mention  nor  did  I 
find  fibrin  or  hemorrhages  in  this  situation  save  in  case  27,  where 
hemorrhage  continuous  with  that  in  the  mucosa  was  found.  Flexner 
says  also  that  the  submucosa  may  be  affected  with  an  intact  or  almost 
intact  mucous  membrane,  while  in  my  cases,  when  the  submucosa 
participated  in  the  process,  it  was  only  when  the  mucous  membrane 
was  greatlv  damaged.  Case  3  is  an  exception  to  this  rule,  the  sub- 
mucosa being  a  little  affected  while  the  mucosa  was  practically  normal. 
Flexner  does  not  speak  of,  but  Strong  and  Musgrave  mention  sub- 
acute  cases   with  hyperplasia  of  the   solitary  follicles   and   superficial 


]  16  John  Howland. 

erosions  which  suggest  my  group  (B)  with  the  follicular  excavations. 
The  other  varieties  that  I  have  described  find  no  prototypes  in  the 
published  reports  of  Manila  cases. 

The  foregoing  report  shows  unmistakably  that  cases  of  Shiga  bacil- 
lus infection  exhibit  most  diverse  pathological  anatomy.  The  gross 
and  microscopical  changes  of  the  extremes  of  these  cases  are  so  differ- 
ent that  at  first  sight  it  would  seem  scarcely  probable  that  they  are 
caused  bv  the  same  micro-organism.  There  are,  indeed,  many  con- 
siderations which  must  be  taken  into  account  before  a  final  opinion 
is  passed  upon  the  question  as  to  what  extent  the  lesions  found  are 
to  be  ascribed  to  the  action  of  this  bacillus. 

It  seems  to  me  that  in  discussing  this  point,  which  is  among  the 
most  important  of  all.  we  cannot  afford  to  disregard  the  facts  of  clin- 
ical observation.  A  moment's  reflection  on  the  clinical  course  of  the 
diarrheas  of  infants  brings  forcibly  to  our  attention  the  common 
observation  that  some  cases  are  extremely  mild  and  respond  almost 
immediatelv  to  ordinary  therapeutic  measures.  In  conformity  with 
this  fact  it  can  be  stated  on  the  basis  of  my  observations  that  a  large 
percentage  of  fatal  cases  fails  to  show  evidence  of  profound  structural 
lesions.  In  view  of  the  slight  nature  of  these  lesions  the  question 
arises  as  to  what  extent  the  infection  is  to  be  regarded  as  a  cause 
of  death  in  infants.  As  regards  this  question  it  may  be  said  imme- 
diately that  among  these  cases  a  certain  percentage  must  be  looked 
upon  as  intercurrent,  or  so-called  terminal  infections  in  children  al- 
ready debilitated  by  previous  disease,  whereas  in  the  remainder  the 
fact  that  the  children  were  institutional  children  in  a  very  depreciated 
state  of  health  must  be  considered.  It  seems  to  me.  therefore,  that 
these  slighter  grades  of  infection  in  more  vigorous  infants  are  pos- 
sibly the  ones  which  respond  so  promptly  to  remedial  measures. 

In  considering  the  severer  lesions,  particularly  the  ulcerative  ones, 
the  question  immediately  arises  as  to  what  extent  the  entire  process 
is  to  be  regarded  as  due  to  the  Shiga  bacillus.  We  are  here  confronted 
with  the  identical  problem  that  has  to  be  considered  in  dealing  with 
similar  infections  in  adults,  and  thus  far  it  has  not  been  possible  to 
separate  sharply  the  damage  done  by  the  Shiga  bacillus  and  that 
which  is  subsequently  done  by  the  entire  host  of  micro-organisms, 
pvogenic  and  others,  normally  contained  in  the  intestinal  tract.  This 
much,  however,  may  be  said :  The  evidence  favors  the  belief  that  the 
primary  necrotic  lesion  is  the  result  of  the  action  of  the  bacillus  of 
dysentery,  the  subsequent  ulceration  being  brought  about  not  im- 
probably by  the  interaction  of  various  micro-organisms  and  the  ordinary 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  117 

processes  of  demarcating  inflammation.  Beyond  this  point  it  does  not 
seem  possible  to  distinguish  the  action  of  the  various  micro-organisms 
in  the  intestine.  The  lesions  in  the  intestine  in  children  as  in  adults 
must  for  the  present  be  conceived  to  be  of  two  kinds;  first,  those  due 
to  the  action  of  the  dysentery  bacillus,  as  already  explained,  and,  sec- 
ond, of  toxic  products  of  this  and  perhaps  other  organisms,  as  is  shown 
by  the  lesions  of  the  submucosa  and  elsewhere.  In  this  regard  there 
is  a  uniformity  in  the  conditions  found  in  children  and  in  adults. 

It  is  important  to  take  cognizance  of  the  fact  that,  after  all,  in  my 
cases  the  lesions  found  were  not  usually  typical  pseudomembranous 
inflammations ;  the  pseudomembrane  appeared  either  on  the  surface  of 
ulcers  or  as  isolated  areas  upon  the  mucous  surface  of  the  intestine. 
In  this  regard  the  changes  in  children  seem  to  be  in  contrast  to  those 
thus  far  described  in  adults.  But  a  still  further  distinction  is  found 
in  the  much  more  common  involvement  of  the  solitary  and  agminated 
lymphatic  structures  in  children — the  same  structures  in  adults  usually 
escaping. 

If  we  endeavor  to  sum  up  the  case  as  here  made  out  for  the  Shiga 
bacillus  we  shall  have  to  say  that  there  are  comprised  under  the  lesions 
associated  with  it  all  grades  and  types  of  diarrheal  disease,  as  dis- 
tinguished by  clinical  symptoms  and  pathological  findings,  and  that 
it  can  be  affirmed  that  no  particular  type  of  such  disease  is  distin- 
guished from  the  others  by  a  special  etiological  origin. 

1.  Centralblatt  fur  Bact.  u.  Parasiten.,  1898,  XXIII,  599. 

2.  Deutsche  Med.  Wochen,  1901,  XXVII,  784. 

3.  Middleton-Goldsmith  Lecture,  1900. 

4.  Report  of  the  Surgeon-General  of  the  Army,   1900. 

5.  American  Medicine,  1902,  IV,  417. 

6.  The  lournal  of  Medical  Research,  Vol.  X,  No.  I. 

7.  Martini  und  Lenz.     Zeitschrift  f.  Hygiene  u.  Infectionkrank,  1902,  XVI, 

559- 

8.  Lenz.     Ibid.,  540. 

9.  Univ.  of  Penna.  Medical  Bulletin,  Vol.  XVI,  Nos.  5-6. 
10.  The  Journal  of  Medical  Research,  Vol.   IX,   No.  2. 


A  REPORT  OF  THE  AGGLUTINATION  REACTIONS  OF  THE 

BACILLUS  DYSENTERIC  WITH  THE  BLOOD  SERUM 

OF  INFANTS  SUFFERING  FROM  DIARRHEA. 

BY    CHARLES    K.    WINNE,    JR.,    M.D., 
Baltimore. 

(From  the  Thomas  Wilson  Sanitarium  for  Sick  Children.) 

The  following  summary  is  a  record  of  the  routine  examination  of 
the  blood  for  agglutination  with  B.  dysenteriae  which  was  carried 
out  at  the  Sanitarium  during  the  summer  of  1903.  It  does  not,  un- 
fortunately, include  all  patients  treated  at  the  Sanitarium  for  in  some 
•instances  blood  was  not  obtained  and,  in  others,  the  pressure  of  the 
usual  clinical  work  prevented  the  examinations  from  being  made. 

The  report  is  based  upon  the  examination  of  100  patients.  The  ma- 
jority were  studied  once,  but  in  a  few  instances  two  or  more  ex- 
aminations were  made.  Forty-five  cases  yielded  positive  and  fifty-five 
negative  results.  No  result  is  recorded  as  positive  unless  the  reaction 
occurred  at  a  minimal  dilution  of  1  :ioo.  When  possible  the  dilutions 
in  every  case  were  carried  up  to  1  :iooo  or  farther. 

The  cases  studied  have  been  divided  into  groups  according  to  the 
symptoms  presented  or  the  discovery,  in  cultures,  of  the  bacillus  of 
dysentery.  For  the  present  I  am  following  the  suggestions  of  Dr. 
Knox  in  denominating  the  cases  in  which  the  bacteriological  findings 
were  positive  as  "Dysenteria  infantum."  The  other  classes  are  those 
generally  recognized.  The  following  table  expresses  the  results  of  the 
blood  examination  according  to  this  view : 


Number 
of  Cases. 

Blood    Examination. 

Number 
Positive. 

Number 
Negative. 

40 
42 

4 
11 

3 

26 

12 

2 

5 
0 

J4 

3" 
2 
6 

3 

100 

45 

55 

Studies  of  the  Diarrheal  Diseases  of  Infancy.  119 

This  table  is  chiefly  valuable  in  excluding  the  cases  of  simple  diar- 
rhea from  the  group  of  cases  yielding  positive  reactions.  Unfortunate- 
ly the  technical  difficulties  of  dealing  with  stools  in  which  the  bacillus 
of  dysentery  is  sought  are  still  too  great  to  permit  of  a  classification 
of  the  disease  being  based  upon  the  results  of  the  bacteriological  ex- 
aminations. The  general  character  of  the  agglutination  reaction  as 
regards  the  above  more  or  less  arbitrary  grouping  of  the  cases  arouses 
suspicion  immediately  of  the  reliabilitv  of  the  cultural  tests  taken  alone. 
As  bearing  on  this  statement  the  negative  reactions  which  have  been 
noted  in  cases  from  which  the  bacillus  of  dysentery  had  been  isolated 
may  be  cited.  Whether  or  not  repeated  testing  of  the  blood  might  not 
have  changed  this  result  cannot,  of  course,  be  stated.  An  analytical 
study  of  the  five  cases  of  malnutrition  and  marasmus  giving  positive 
reactions  yields  the  following  data :  Two  cases  had  bloody  stools  in  the 
spring;  one  gave  a  history  of  an  intermittent  diarrhea  lasting  two  or 
three  months,  and  one  had  a  marked  mucous  diarrhea  on  entrance. 

As  regards  the  day  of  disease  upon  which  a  positive  reaction  was 
obtained  the  earliest  ones  were  on  the  second  day  and  third  days 
— 1  :iooo  dilution.  Other  early  reactions  were  obtained  on  the  5th, 
7th,  8th,  and  9th  days.  Eight  cases  gave  negative  results  on  the  25th 
or  30th  day :  of  these,  two  cases  returning  with  relapse,  were  then 
positive. 

The  persistence  of  the  reaction  was  found  to  be  variable.  One  case 
positive  on  the  5th  day  was  negative  on  the  31st  day.  Other  cases  were 
positive  for  longer  periods.  Two  cases  which  had  suffered  from 
bloody  diarrhea  three  months  before  admission  to  the  sanitarium  for 
malnutrition  still  gave  reactions  in  1  :ioo  to  1  :25c  dilutions.  Dysentery 
bacilli  were  isolated,  at  this  time,  by  Bassett  from  both  cases. 

The  limits  of  agglutination  in  44  cases  were  as  follows:  1:100,  13 
cases;  1  :25o,  3  cases;  1  :500,  5  cases;  1  :iooo,  22  cases;  1  :i500,  1  case. 
In  general  it  may  be  stated  that  the  height  of  the  reaction  is  in  part 
determined  by  the  degree  of  seeding  of  the  suspension  of  bacteria — a 
light  seeding  often  reacting  higher  than  a  heavier  one.  On  the  other 
hand,  a  quicker  reaction  could  often  be  obtained  with  the  heavier  sus- 
pensions than  with  the  lighter  ones. 

It  is  to  be  regretted  that  time  was  not  allowed  for  working  with  the 
different  types  of  the  organism.  All  the  tests  were  made  with  the 
Flexner-Harris  bacillus  although  two  strains  of  this  bacillus  were  em- 
ployed since  it  was  found  that  a  recent  isolation  from  one  of  our  cases 
gave  more  satisfactory  results  than  the  old  stock  cultures  of  the  "Har- 
ris" organism  isolated  by  Flexner  in  Manila.     However,  the  choice 


120  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

of  this  type  of  the  bacillus  for  the  tests  was  made  on  the  basis  of 
Gay's  demonstration  of  the  mannite  fermenting  properties  of  the  or- 
ganisms isolated  the  previous  summer  by  Duval  and  Bassett;  and  this 
choice  seemed  to  be  justified  by  the  fact  that  the  dysentery  bacillus 
isolated  by  Bassett  during  the  past  summer  (1903)  from  the  cases  in 
the  sanitarium,  including  those  of  this  report,  consisted  entirely  of  this 
form  of  the  bacillus. 

The  reactions  were  observed  at  one  hour  and  at  three  hours,  or  in  a 
few  cases  at  four  or  five  hour  intervals.  Of  the  positive  cases  18  re- 
acted in  one  hour  and  26  at  the  later  period.  Some  of  the  higher 
dilutions  were  disregarded  at  the  second  reading  because  of  the  multi- 
plication and  overgrowth  of  the  bacilli. 

Of  the  44  positive  cases  23  showed  blood  in  the  stools  while  at  the 
sanitarium  or  gave  a  history  of  blood  sometime  during  the  illness.  All 
cases  except  two  showed  mucus  and  a  few  cases  pus  in  considerable 
quantity.  Of  the  42  cases  in  which  blood  was  present  in  the  stools.. 
24  gave  positive  agglutination  reactions.  Among  the  18  negative  cases 
were  manv  of  those  tested  earlv  in  the  course  of  the  disease. 


DISCUSSION   AND   CONCLUSIONS. 

SIMON  FLEXNER,  M.D. 

The  foregoing  reports  of  an  investigation  into  the  bacteriology  of 
the  diarrheal  diseases  of  children  call  for  a  word  of  discussion.  Each 
report  states  with  precision  and  in  some  detail  the  circumstances  under 
which  the  task  of  investigation  was  conducted,  from  which  an  impres- 
sion is  immediately  obtained  of  the  strong  bias  under  which  the  ex- 
aminations were  made.  The  purpose  of  the  investigation  was  not, 
indeed,  the  renewed  exhaustive  study  of  the  bacterial  flora  of  the  dis- 
charges of  these  children,  but  was  the  testing  of  the  definite  question 
of  the  presence  and  distribution  of  Bacillus  dysenteriae,  with  which 
microorganism  Duval  and  Bassett  had  the  previous  summer,  while 
working  under  a  grant  from  the  Rockefeller  Institute  for  Medical  Re- 
search, associated  in  a  causal  relation  certain  of  these  diarrheal  states. 
Since  the  supposed  etiological  significance  of  this  pathogenic  bacillus 
could  best  be  tested  further  by  an  extensive  study  of  the  facts  and  con- 
ditions of  its  occurrence  in  different  localities  in  children  ill  of  diarrhea, 
the  investigation  was  planned  to  accomplish  this  purpose. 

In  the  carrying  out  of  such  a  collective  investigation  it  could  not 
be  expected  that  no  external  factors  would  enter  to  affect  the  agree- 
ment of  the  final  results.  Perhaps  the  factor  that  would  operate  chiefly 
in  this  respect  is  the  relative  experience  of  the  different  workers  in 
dealing  with  the  problems  before  them.  I  think  myself  fortunate  in 
having  been  able  to  secure  so  large  a  number  of  bacteriologists  who 
entered  into  the  work  assigned  them  with  spirit,  energy  and  determina- 
tion ;  but  I  realized  at  the  outset  that  the  experience  gained  by  certain 
of  the  workers  at  previous  times  in  the  very  field  which  they  were  now 
to  re-enter  gave  them  great  advantages  over  their  colleagues  who 
started  upon  the  difficult  task  of  separating  the  bacterial  flora  of  the 
intestinal  discharges  after  a  few  weeks  of  hurried  preparation  in  its 
methods  and  in  the  special  study  of  the  bacillus  of  dysentery.  Hence, 
in  summing  up  the  evidence  for  and  against  this  microorganism  as  a 
possible  cause  of  the  diarrheal  disease  of  children,  in  so  far  as  the  re- 
sults of  this  investigation  may  be  taken  as  affecting  that  evidence,  ac- 
count should  be  taken  of  the  methods  of  its  recovery  which  are,  up  to 


122  Simon  Flexner. 

the  present,  so  imperfect  that  in  the  hands  of  one  set  of  competent 
bacteriologists  failure  in  50  per  cent,  of  the  instances  will  occur,  while 
the  same  methods  in  other  and  more  specially  instructed  hands  will 
yield  successful  isolation  in  practically  every  case  in  which  it  is  sought. 
I  draw  attention  to  this  discrepancy,  while  at  the  same  time  I  am 
emphasizing  the  wide  distribution  of  the  bacillus  established  by  these 
studies,  for  I  conceive  that  both  are  arguments  for  a  causative  role 
which,  while  containing  something  of  strength,  contain  also  something 
of  weakness. 

That  the  character  of  the  materials  in  which  the  bacillus  is  sought 
affects  the  result,  all  workers  are  agreed;  but  the  experience  of  last 
summer  (1903)  has  been  convincing  in  showing  that  this  factor  is  less 
important  than  the  studies  of  Duval  and  Bassett  seemed  to  indicate. 
And  yet  their  view  is  still  in  part  to  be  upheld,  for  in  relative  ease  of  re- 
covery the  particular  kind  of  discharges  with  which  they  operated 
chiefly — those  containing  mucus  and  blood  and  fairly  free  of  fecal  mat- 
ter— far  exceeds  the  more  common  mixture  of  mucus  and  feces  which 
constituted,  in  this  study,  the  larger  part  of  the  morbid  specimens  ex- 
amined. The  mere  presence  of  blood  in  the  stools  is  of  less  moment 
than  Duval  and  Bassett  supposed ;  but  feces  or  undigested  food  are 
when  present  distinct  obstacles,  apparently,  to  the  isolation  of  the  ba- 
cillus. Hence  a  second  important  factor  which  affects  the  general  re- 
sults to  be  considered  in  this  review  is  the  varied  nature  of  the  materials 
subjected  by  the  different  workers  to  bacteriological  examination. 

A  third  factor,  and  one  of  considerable  moment,  has  to  do  with  the 
manner  of  collection  of  the  morbid  material  and  the  promptness  with 
which  it  is  distributed  in  the  Petri  plates.  Just  as  feces  and 
food  make  the  isolation  of  the  bacillus  of  dysentery  more  difficult  by 
introducing  into  the  plates  a  larger  number  of  intestinal  and  extraneous 
bacteria,  that  in  their  turn  either  dilute  the  former  organisms  individu- 
ally, or  through  their  presence  and  products  restrict  the  growth  of  the 
dysentery  bacillus,  so  in  the  same  manner  do  the  extraneous  bacteria  of 
unclean  napkins  and  parts  interfere  when  present  with  its  recovery. 
And  as  multiplication  of  the  bacteria  contained  in  the  discharges  con- 
tinues outside  the  intestine,  and  fails  to  proceed  equally  in  all  kinds 
but  more  in  one  kind  than  another,  it  chances  that  the  bacillus  of 
dysentery,  under  these  invidious  conditions,  is  soon  overgrown  and 
rendered  more  difficult  of  isolation.  Thus  it  happens  that  the  circum- 
stances under  which  the  examinations  were  conducted. — the  proximity 
or  removal  of  the  laboratory  from  the  source  of  the  specimens,  the 
manner  of  collection  of  the  latter,  and  the  rapidity  with  which  they 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  123 

could  be  dealt  with  in  the  laboratory — will  be  found  to  have  had  a 
marked  and  unmistakable  influence  upon  the  individual  results.  To 
cite  a  case  in  point :  Gay  and  Stanton's  figures  show  that  the  material 
obtained  from  Bellevue  Hospital  under  what  are  to  be  regarded  as  fa- 
vorable conditions  gave  a  percentage  of  successes  almost  3  times  as 
great  as  was  obtained  from  the  distinctly  unfavorable  specimens,  for 
the  purposes  of  this  study,  supplied  from  the  tenement  district  in  which 
none  of  the  necessary  precautions  in  collection  could  be  carried  out,  and 
an  unavoidably  long  interval  of  time  elapsed  between  the  passage  and 
the  making  of  the  plates  at  the  laboratory.  In  keeping  with  this  dis- 
crepancy is  the  fact  that  the  plates  of  the  one  series  (Bellevue)  were 
practically  free  from  extraneous  bacteria  while  those  from  the  other 
series  (tenement  district)  were  often  grossly  contaminated. 

There  can  be  no  doubt  that  the  discharges  do  not  as  a  rule  contain 
the  bacilli  of  dysentery  in  such  numbers  or  combinations  as  make  pos- 
sible their  recovery  as  readily  or  in  as  large  numbers  as  from  the'  in- 
testinal mucosa.  I  drew  attention  to  this  fact  on  the  basis  of  my 
studies  of  acute  tropical  dysentery  (Manila),  and  it  has  been  confirmed 
by  the  studies  of  Vedder  and  Duval  upon  institutional  dysentery  in 
this  country  as  well  as  by  Duval  and  Bassett  in  their  study  of  children 
in  1902.  A  further  confirmation  is  found  in  the  foregoing  reports  of 
Bassett  and  of  Wollstein  and  Dewey.  It  is  of  interest  to  note  that 
gentle  scraping  of  the  rectal  mucosa  during  life  will  yield  material 
from  which  the  dysentery  bacillus  may  be  recovered  when  it  has  not 
been  isolated  from  the  natural  intestinal  discharges,  and  the  most  con- 
stant results  are  obtained  from  deeper  scrapings  of  the  mucosa  of 
the  intestine  post  mortem,  the  autopsy  having  been  made  soon  after 
death. 

This  intimate  relationship  of  the  bacillus  of  dysentery  to  the  sub- 
stance of  the  mucosa  of  the  intestine,  in  which  locality,  under  pathologi- 
cal conditions,  at  least,  it  seems  easily  able  to  survive  and  multiply,  is  of 
considerable  significance ;  and  the  reverse  fact  which  teaches  that  this 
organism  increases  far  less  readily  and  is  quickly  overgrown  in  dis- 
charges when  once  outside  the  body,  can  be  interpreted  as  indicating 
that  it  is  less  well  adapted  for  a  saprophytic  than  for  a  parasitic  exist- 
ence. The  bearing  which  these  data  must  have  upon  our  views  of  the 
pathogenic  properties  of  the  bacillus  of  dysentery  need  not  be  especially 
emphasized. 

In  the  course  of  the  investigation  carried  on  during  the  summer,  412 
cases  of  diarrheal  disease  among  children  were  studied  bacteriologically 
with  reference  to  the  presence  of  the  bacillus  of  dysentery.   Of  this 


124 


Simon  Flexner. 


number  positive  results  were  obtained  in  279  or  in  63.2  per  cent,  of 
all  cases  examined.  Since  these  figures  are  made  up  from  the  totals  of 
all  the  reports  a  glance  at  the  following  table  will  show  the  manner  in 
which  they  have  been  secured.  And  when  it  is  remembered  that  the 
cases  studied  were  not  as  a  rule  selected  but  taken  as  they  entered  hos- 
pitals and  dispensaries,  the  prevalence  of  the  bacillus  of  dysentery  in 
children  is  no  less  than  remarkable. 


Number 
of  Cases 

Studied. 

B.  Dysenteric  Present. 

B.  Dysenterias  Absent. 

Investigator. 

Number  of 
Cases. 

Per  cent. 

Number  of 
Cases. 

Per  cent. 

79 
73 
62 

5i 
47 
31 

21 

20 
28 

75 
51 
48 
26 

19 
29 
11 

13 

7 

94- 
70. 
78. 

51- 
40. 
93-5 
52.5 

65. 

25- 

4 
22 

14 
25 
28 
2 
10 

7 
21 

6 

30- 
22. 

49- 
60 

Wollstein  and  Dewey 

Waite 

Kendall 

6.5 
47-5 

35- 

75- 

Gay   and   Stanton,      Bellevue 

Gay    and     Stanton,       Tene- 

Total 

412 

279 

63.2 

*33 

36.8 

If  we  turn  our  attention  now  to  the  character  of  the  discharges  used 
in  the  investigation  we  will  be  struck  with  the  great  preponderance  of 
mucus  and  fecal  specimens  over  those  in  which  blood  and  mucus  were 
contained : 


Investigators. 

Total  Number  of 
Stools  Reported. 

Blood  and 

Mucus.* 

Mucus. 

1 
Mucus  and       Feces 
Feces.     1     Alone. 

79 
64 
60 

5i 
48 

43 
3l 
21 

25 
26 
20 

9 
12 
16 

5 
7 

15 
19 
0 

0 
1 

0 
1 
0 

36 
17 

40 

33 
35 
26 

25 
14 

3  (?) 
2  (?) 

9 

Wollstein  and  Dewey. . . . 

Waite 

Kendall 

Total 

397 

120 

36 

226 

15 

*  With  or  without  feces. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


125 


Thus  of  397  specimens  of  intestinal  discharges  reported  considerably 
less  than  one-third  contained  blood  in  quantities  appreciable  to  the  naked 
eye.  This  table  is  by  itself  incomplete,  for  what  is  required  before  any 
conclusions  can  be  drawn  of  the  relation  of  the  character  of  the  dis- 
charges to  the  occurrence  of  Bacillus  dysenteriae  is  the  relative  propor- 
tion of  the  stools  of  different  kinds  which  were  associated  with  the 
organism  as  proven  by  cultural  tests.  The  next  table  has  been  prepared 
to  express  this  association  and  gives  the  exact  figures  as  far  as  they  can 
be  gathered  from  the  reports. 


Investigators. 

Total    Number   of 

Positive  Results 

from   Stools. 

Blood  and 
Mucus. 

Mucus. 

Mucus  and 
Feces. 

Feces. 

Duval    and  Shorer. . . . 
Bassett 

74 
43 
46 
26 
20 
16 

29 
1 1 

21 
19 
17 
6 
6 
9 
5 
5 

J3 

10 
0 
0 
1 
0 
1 
0 

38 
14 
29 
18 
'3 

7 
23 

0 

2  (?) 
0 

Wollstein  and  Dewey. . 

0 

2  (1?) 

Waite 

0 
0 

Kendall 

0 

0 

Total 

265 

88 

25 

148 

4 

This  table  confirms  the  preceding  one  since  it  exhibits  that  the  pro- 
portion of  specimens  containing  visible  blood  and  constituting  so-called 
''positive''  discharges  is  about  one-third  of  the  whole  number  yielding  in 
culture  Bacillus  dysenteriae,  and  it  further  bears  out  the  statement  made 
in  the  early  parts  of  this  review,  namely,  that  the  larger  part  of  the 
specimens  from  which  the  bacillus  of  dysentery  was  isolated  were  not 
admixed  with  blood.  In  view  of  this  finding  it  could  be  predicted  that 
the  muco-fecal  stools  would  head  the  list  of  instances  of  successful 
recovery ;  and  it  is  also  important  to  observe  what  has  hitherto  been 
overlooked,  that  in  at  least  three  instances  (one  example  doubtful — 
probably  feces  diluted  with  serum)  the  bacillus  of  dysentery  was  secured 
from  fecal  material  in  which  neither  blood  nor  mucus  was  detected. 

It  is  not  my  intention  to  discuss  the  bearing  of  these  facts  and  find- 
ings upon  the  clinical  types  of  the  diarrheal  diseases  of  children.  For- 
tunately many  of  the  cases  were  carefully  observed  by  clinicians  whose 
records  will  serve  the  purpose  of  correlating  the  results  of  the  bacterio- 
logical examinations  with  the  clinical  features  presented  by  the  children. 
This  part  of  the  present  investigation  will  be  dealt  with  in  another  por- 
tion of  this  publication. 


126  Simon  Flexner. 

When  we  stop  to  consider  the  wide  distribution  in  children  of  the 
bacillus  of  dysentery,  which  is  proved  by  this  study,  the  question  of 
the  natural  habitat  of  the  organism  and  its  mode  of  entrance  into  the 
body  arises  in  our  minds.  Unfortunately  our  knowledge  upon  the 
habitat  of  the  bacillus  is  practically  nil.  The  bacillus  has  not  yet  been 
found  in  our  surroundings  and  is  known  only  as  occurring  in  the  in- 
testine and  very  rarely  elsewhere  in  human  beings.  The  facts  with 
reference  to  its  pathogenicity,  as  they  appear  from  the  investigations  of 
outbreaks  of  bacillary  dysentery  in  adults,  would  lead  us  to  suppose 
that  it  led  a  parasitic  existence  in  the  body  of  human  beings  and  was 
scarcely  to  be  sought  among  the  saprophytes  of  the  intestine.  But 
the  broader  fact  that  the  organism  occurs  in  children  who  may  be 
very  little  ill  compels  us  to  examine  more  carefully  and  openly  into  the 
assumption  of  a  purely  parasitic  existence,  which  we  have  hitherto 
and  perhaps  tacitly  made  in  regard  to  the  dysentery  bacillus. 

It  has  of  course  occurred  to  all  investigators  of  the  pathological 
conditions  supposed  to  be  due  to  the  dysentery  bacillus  to  search  for 
the  organism  in  healthy  persons.  Shiga,  Flexner,  Kruse,  Duval  and 
Bassett  and  Wollstein  have  in  turn  sought  the  organism  in  the  dis- 
charges of  healthy  adults  or  children  unsuccessfully.  But  the  experi- 
ences of  the  past  summer  called  for  renewed  and  painstaking  investiga- 
tions of  this  question,  and  hence,  at  my  request.  Dr.  Wollstein  and  Dr. 
Duval  attacked  it  afresh.  At  Dr.  Welch's  suggestion  I  had  Dr.  Duval 
search  for  the  organism  in  infants  to  whom  mild  cathartics  had  been 
administered  with  the  result  that  he  isolated  it  in  very  small  numbers 
from  the  stools  of  two  healthy,  milk-fed  children.  The  few  colonies 
obtained  gave  the  reactions  of  the  "Flexner-Harris"  bacillus. 

I  do  not  intend  to  dwell  long  on  this  finding  which  calls.  I  think,  for 
confirmation  from  a  wide  and  varied  material  drawn  from  human 
beings  in  health  and,  perhaps,  in  other  intestinal  diseases  than  those 
in  which  the  organism  has  now  been  found.  That  the  diarrheal  dis- 
eases of  a  definitely  foreign  and  specific  origin,  e.g.,  tuberculosis,  may 
not  yield  the  bacillus  of  dysentery  even  after  prolonged  search  is  in- 
dicated by  Kendall's  report  upon  two  instances  of  tuberculous  enteritis. 

The  unexpected  finding  of  the  bacillus  of  dysentery  in  healthv  in- 
fants and  the  wide  occurrence  of  that  organism  in  the  common  form  of 
diarrhea  in  children,  open  up  a  considerable  field  of  speculation  upon 
the  real  pathological  significance  of  the  organism.  It  would  seem  as  if 
we  had  no  grounds  for  denying  it,  in  many  pathological  cases,  signifi- 
cance ;  for  the  presence  of  the  agglutination-reaction,  the  increasing 
number  of  the  organisms  in  the  discharges  and  their  close  relationship 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  127 

to  the  intestinal  mucosa  in  such  cases  afford  ample  proof  of  its  patho- 
genic action.  Since  these  data  have  been  considered  convincing  with 
reference  to  adult-infections  they  will  hardly  be  denied  application  in 
the  cases  of  the  children  we  are  now  considering. 

A  point  of  difference  in  the  mode  of  spread  of  the  adult  and  children 
infections  is  at  first  sight  apparent.  While  the  former  often  extend 
with  epidemic  severity,  the  latter  do  not  present  the  features  of  spread- 
ing epidemic  infections.  The  cases  of  infection  in  children  seem  to  be 
examples  of  individual  inoculation,  although  occasional  examples  of 
contagion — from  child  to  child — occur  as  in  the  instance  recorded  by 
Bassett.  However,  the  corresponding  occurrence  of  sporadic  infection 
among  adults  is  also  established  as  in  the  cases  studied  in  this  country 
by  Vedder  and  Duval  and  later  by  Gay  and  Duval.  And,  moreover, 
the  endemic  bacillary  dysentery  of  the  tropics  which  does  not  flourish 
as  an  epidemic  disease  but  as  an  individualistic  one  arising  from  a  com- 
mon source,  presents  some  of  the  striking  epidemiological  characters 
of  the  infections  in  children  that  we  are  discussing. 

When  we  turn  our  attention  to  the  probable  source  of  the  infecting 
bacillus  in  children  we  appreciate  immediately  our  entire  ignorance 
of  the  habitat  in  nature  of  the  organism.  Whether  it  gains  access  to 
the  intestinal  tract  with  milk,  water  or  other  substances  we  can  only 
conjecture.  But  it  is  among  the  possibilities  that  the  bacillus  of  dysen- 
tery is,  after  all,  an  occasional — perhaps  a  constant? — inhabitant  in 
some  districts  of  the  intestinal  canal  where  it  survives  saprophytically 
among  the  other  intestinal  bacteria.  If  such  a  possibility  be  admitted 
then  it  might  also  be  considered  whether  a  whole  host  of  insults  to  the 
intestinal  mucosa  or  functions  may  not  allow  the  less  restrained  growth 
of  the  organism  and  eventually  the  acquisition  of  parasitic  and  invasive 
properties  which  could  lead  to  more  or  less  serious  pathological  dis- 
turbances. 

In  bringing  forward  this  speculation  I  am  not  unmindful  of  its  bear- 
ing upon  our  knowledge  of  those  endemic  and  epidemic  infections  in 
which  there  can,  I  think,  be  no  doubt  of  the  importation  from  without 
of  a  highly  pathogenic  organism  preceding  the  outbreak  of  symptoms. 
That  two  modes  of  infection  may  occur — auto-infection  and  extra-in- 
fection— is  not  inconsistent  with  our  knowledge  of  other  diseases.  I 
need  only  refer  to  the  lobar  pneumonias  in  which  the  abiding  micro- 
coccus lanceolatus  of  the  saliva  may  be  the  exciting  cause  or 
as  in  house  and  institutional  epidemics  of  that  disease,  a  more  intensely 
pathogenic  organism  taken  into  the  body  from  surrounding  persons 
or  things  mav  be  the  direct  source  of  contagion.     I  shall  not  pursue 


128  Simon  Flexner. 

this  line  of  argument  further ;  and  I  mean  to  content  myself  with  the 
observation  that  we  must  be  willing  to  admit  for  the  bacillus  of  dysen- 
tery, what  we  have  come  to  admit  for  many  other  pathogenic  species  of 
microorganisms, — e.g.,  cholera  bacilli,  tubercle  bacilli,  pneumococci, 
diphtheria  bacilli  and  pus  cocci — namely,  the  influence  of  other  fac- 
tors than  the  mere  presence  of  the  injurious  bacillus  in  determining 
the  origin  of  infection.  That  the  bacillus  of  dysentery  has  a  wide  dis- 
tribution in  children  may  be  taken  as  established  by  this  investigation; 
but  whether  in  every  instance  in  which  it  has  been  found  it  is  to  be 
considered  as  acting  in  a  pathogenic  manner  and  hence  is  to  be  regarded 
as  the  prime  or  even  proximate  cause  of  all  existing  intestinal  lesions, 
are  questions  to  which  final  answers  are  not  yet  to  be  given. 

It  is  not  without  theoretical,  perhaps  not  without  practical  interest, 
that  the  type  of  bacillus  which  prevails  in  children  is  that  obtained  by 
Flexner  from  certain  cases  of  Philippine  dysentery.  This  "Flexner- 
Harris"  type  of  the  organism  was  found  in  the  great  majority  of  all  the 
children  from  whom  dysentery  bacilli  were  isolated,  and  in  the  experi- 
ence of  certain  of  the  investigators  was  the  only  type  met  with.  A 
statement  of  the  figures  will  best  exhibit  the  comparative  frequency  of 
prevalence  of  the  two  types  : 


Investigators. 

Total    Number    of 

Cases    Yielding   B. 

Dysenteria?. 

Number  Yielding    Number    Yielding 
"  Shiga"  Type     /'Shiga"  and  "Flex- 
Alone.              ner-Harris  "  Types. 

75 

2Q 
1  I 

]9 

20 
26 
4» 

5' 

11                                     6 

Kendall 

4                                     0 

3                                       0 
2                                      0 
2                                      0 
1                                      0 

Since  the  cases  of  the  "Shiga"  type  of  infection  are  so  unusual,  it  will 
be  worth  while  to  examine  the  records  in  order  to  determine  whether 
they  present  any  features  which  may  be  regarded  as  peculiar.  It  may 
add  to  the  clearness  of  the  matter  to  speak  of  the  cases  as  consisting  of 
"single"  and  "double"  infections.  Thus  we  shall  have  single  infec- 
tions with  the  "Flexner-Harris"  or  "Shiga"  type  of  bacillus  or  double 
infections  in  which  both  types  are  associated.  The  following  table 
shows  the  number  of  "Shiga"  bacilli  obtained  from  the  plates  and  their 
relation  to  the  associated  "Flexner-Harris"  type,  as  well  as  the  nature 
of  the  discharges  yielding  them. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


129 


en 
m 

u 

>-c  in  x) 

u|-= 

ScgS 

Number  of 

0  -    u 

Description  of    Material  Yield- 

Investigator. 

7  0  a"S 

£->  —'   in  7" 
_  O  s0h 

5  U  *  S 

Col oni  es 
of  "Shiga" 
Type. 

JO    ~^ 

—      7}        1 

E    1)    u    <U 

ing  "Shiga"  Type. 

S.—  Stool. 

- 

o^^o 

3-S  «  Q. 

Z 

hohi 

2   0  B>P 

7 

Duval   and 

Shorer 

Not  stated 

2 

2 

s. 

Mucus  and  feces;  brown  semi- 
solid. 

8 

Duval   and 

Shorer 

Not  stated 

1 

7 

S. 

Yellow  mucus. 

XI 

Duval  and 

Shorer 

Not  stated 

2 

5 

S. 

Muco-fecal. 

13 

Duval  and 

Shorer 

Not  stated 

28 

2* 

S. 

Green  muco-fecal;    little   blood. 

15 

Duval   and 

Shorer 

Not  stated 

1 

0 

S. 

Blood-flecked  mucus. 

17 

Duval   and 

Shorer 

Not  stated 

1 

0 

s. 

Green,  muco-fecal;  blood- 
flecked. 

'9 

Duval   and 

Shorer 

Not  stated 

3 

1 

S. 

Small,  bloody  mucous. 

3} 

Duval   and 

Shorer 

Not  stated 

34 

0 

S. 

Large,  fluid;   muco-fecal. 

36 

Duval   and 

Shorer 

Not  stated 

3 

0 

S. 

Large,  liquid;  muco-fecal. 

38 

Duval   and 

Shorer 

Not  stated 

2 

4 

S. 

Green,  muco-purulent. 

43 

Duval  and 

Shorer 

Not  stated 

45 

0 

s. 

Yellow  mucus. 

55 

Duval  and 

Shorer 

Not  stated 

4 

0 

s. 

Curds  and  muco-feces. 

56 

Duval  and 

Shorer 

Not  stated 

0 

s. 

Green;    muco-fecal. 

66 

Duval   and 

Shorer 

Not  stated 

1 

0 

s. 

Blood  and  mucus. 

68 

Duval   and 

Shorer 

Not  stated 

1 

0 

s. 

Mucus  and  blood  flecks. 

73 

Duval   and 

Shorer 

Not  stated 

1 

0 

s. 

Blood-flecked  mucus. 

76 

Duval   and 

Shorer 

Not  stated 

8 

0 

s. 

Green ;    muco-fecal. 

1 

Kendall 

Not  stated 

Not  stated 

0 

s. 

Green-yeliow  ;   blood-flecked. 

2 

Kendall 

Not  stated 

Not  stated 

0 

s. 

Green-yellow  fluid. 

3 

Kendall 

Not  stated 

Not  stated 

0 

s. 

Green-yellow   fluid. 

34 

Kendall 

Not  stated 

Not  stated 

0 

s. 

Green-yellow,  semi-solid  ;  mod. 
mucus. 

2 

Lewis 

Not  stated 

1 1 

0 

s. 

Large,  curdy;  mucus  and  feces; 
blood  flecks. 

7 

Lewis 

Not  stated 

14 

0 

s. 

Much  mucus,  some  feces. 

19 

Lewis 

Not  stated 

10 

0 

s. 

Large;  muco-fecal. 

4+ 

Gay  and  Stanton 

Not  stated 

2 

0 

s. 

S  mal  1  quantity  ;      mucus    and 

blood. 

45 

Gay  and  Stanton 

Not  stated 

8 

0 

s. 

Greenish-yellow;      mucus      and 

feces. 

35 

Cordes 

22 

2 

0 

s. 

Soft,  yellow  and  brown;  little 
mucus. 

21 

Waite 

J7 

1 

0 

Rectal  tube;  thin,  mucus  and  blood. 

41 

Waite 

70 

2 

0 

S. 

Pasty,  dried;  blood-flecked. 

*  Mixed  "  Flexner-Harris  "  and  "Y"   type  of  bacillus.     Vide  infra. 


Scrutiny  of  the  table  brings  out  the  absence  of  any  strikingly  pe- 
culiar behavior  of  the  "Shiga"  type  of  bacillus  in  the  plates  and  shows 
that  what  is  true  in  respect  to  the  numerical  occurrence  for  one  type  is 
equally  true  for  the  other  type.  For  the  most  part  the  number  of 
colonies  of  the  "Shiga"  bacillus  isolated  was  small,  although  in  some  in- 
stances it  was  fairly  large.  It  may  be  of  interest  to  note  the  rare 
occurrence  of  double  infections  and  the  preponderance  of  the  "Shiga" 
organism  in  the  examples  of  this  form  of  infection. 

The  table  also  exhibits  the  entire  absence  of  qualities  in  the  dis- 
charges, that  would  serve  to  characterize  this  group  of  cases  as  pe- 
culiar or  different  from  the  general  cases  in  which  the  "Flexner-Har- 


130  Simon  Flexner. 

ris"  type  of  bacillus  occurs  alone.  And  I  am  not  aware  that  the  group 
of  cases  yielding  the  "'Shiga"  type  of  bacillus  presented  distinctive 
clinical  features.  Consequently  we  must,  for  the  present,  look  upon 
the  two  groups  of  cases,  namely  the  one  in  which  the  "Flexner-Har- 
ris" type  of  bacillus  and  the  other  in  which  the  '"Shiga"  type  has 
been  found,  as  of  equal  value  in  regard  to  the  part  played  in  them  by 
the  bacillus  of  dysentery. 

In  order  that  no  misapprehension  of  the  results  may  occur  I  should 
state  that  all  the  investigators  were  on  the  alert  to  discover  cases  in 
which  the  "Shiga"  type  of  bacillus  was  present.  The  desirability  of 
determining  the  types  of  all  colonies  of  the  dysentery  bacillus  obtained 
was  impressed  upon  the  workers,  and  as  each  report  deals  with  the 
matter  of  types  it  is  fair  to  asume  that  no  "Shiga"  colonies  were  over- 
looked by  accident  or  through  omission  of  the  tests. 

Our  present  knowledge  of  the  bacillus  of  dysentery  has  led  us  to 
distinguish  two  related  types  of  bacilli  to  which  the  designations  al- 
ready given  have  been  applied.  But  it  is  not  only  probable,  but  indeed 
proven,  that  by  the  employment  of  additional  physiological  tests  other 
variations  in  behavior  of  bacilli  of  this  general  kind  may  be  detected. 
An  interesting  variation  of  this  nature  has  been  described  by  Hiss  and 
Russell  in  their  bacillus  "Y."  This  bacillus  while  exhibiting  the  gen- 
eral biological  qualities  of  the  "Flexner-Harris"  organism  differs  from 
the  latter  in  failing  to  attack  dextrine  with  the  production  of  acid.  In 
only  one  set  of  the  studies  of  the  summer  was  attention  paid  to  the 
occurrence  of  the  last  named  organism.  At  the  suggestion  of  Dr.  Hiss, 
Duval  and  Shorer  tested  all  the  "Flexner-Harris"  bacilli,  so-called, 
which  they  isolated  from  cultures,  upon  dextrine  and  found,  in  this 
way,  bacillus  "Y"  twelve  times.  With  one  exception  in  all  12  in- 
stances the  organism  was  associated  with  the  "Flexner-Harris"  ba- 
cillus. It  is  of  some  interest  to  note  that  its  numerical  relations  to  the 
"Flexner-Harris"  bacillus  were  as  indefinite  as  was  the  case  with  the 
"Shiga"  type  of  organism;  for  while  in  some  instances  it  formed  only 
a  fraction  of  all  the  colonies  of  B.  dysenteriae  recovered  from  the 
plates  in  others  it  was  the  predominating  organism. 

If  we  pause  for  a  moment  in  order  to  recapitulate  the  types  of  bacilli 
which  are  now  admitted  to  belong  to  the  group  of  B.  dysenteriae  and 
to  consider  the  physiological  properties  upon  which  distinction  is 
based  the  following  data  will  be  obtained  : 

(1)  ""Shiga"  type:  attacks  glucose,  without  action  on  other  sugars 
including  mannite  and  lactose. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  131 

(2)  "Flexner-Harris"  type:  attacks  glucose,  mannite  and  dextrine; 
does  not  attack  lactose. 

(3)  Bacillus  "Y"  (Hiss  and  Russell),  attacks  glucose  and  mannite; 
no  action  on  dextrine  and  lactose. 

In  the  course  of  the  collective  investigations  of  the  past  summer  an- 
other bacillus  was  met  with  by  several  of  the  workers  which,  should 
it  prove  to  belong  to  this  group  of  organisms,  will  constitute,  so  far 
as  physiological  properties  are  concerned,  another  variation.  The 
properties  of  this  bacillus  are  described  in  some  detail  by  Duval  and 
Shorer  although  its  occurrence  is  noted  also  by  Gay  and  Stanton  and 
Kendall.  Duval  and  Shorer  state  that  in  two  cases  a  bacillus  was 
secured  which  agreed  morphologically,  in  staining  properties,  and  in 
the  usual  cultures  with  a  typical  control  culture  of  B.  dysenteriae  and, 
in  addition,  that  it  agglutinated  in  considerable  dilution  with  antidysen- 
teric  serum  from  the  horse.  On  the  other  hand,  its  action  upon  milk 
and  upon  lactose-serum-water  distinguished  it  from  the  types  of  dysen- 
tery bacilli  now  recognized.  The  bacilli  in  question  cause  first  an 
acidity  of  the  milk  which  reaches  its  height  in  (circa)  48  hours,  after 
which  there  is  a  gradual  return  to  alkalinity.  In  this  respect  the  bacil- 
lus resembles  the  usual  cultures  of  B.  dysenteriae.  But  after  a  second 
period  of  5  to  6  days  acidity  again  makes  its  appearance,  exceeds  in 
intensity  the  primary  reaction,  and  is  permanent.  That  the  second 
acidity  arises  from  action  upon  lactose  is  shown  by  the  coagulation  by 
the  bacillus  of  Hiss'  serum-water  to  which  pure  lactose  has  been  added. 
Reference  to  the  epitomized  statement  given  above,  of  the  effect  of  at 
least  three  "types''  of  dysentery  bacilli  upon  several  kinds  of  sugar, 
will  at  once  make  clear  this  distinction  as  none  of  these  attacks  lactose. 

In  view  of  the  variations  in  physiological  properties  which  we  are 
discussing  it  is  worth  pointing  out  that  Duval  and  Shorer  have  sepa- 
rated further  this  anonymous  bacillus  into  two  forms  of  which  one  at- 
tacks and  the  other  is  without  action  upon  dextrin.  In  other  words 
the  same  physiological  differences  exhibited  by  the  "Flexner-Harris" 
bacillus  and  "Bacillus  Y"  are  displayed  by  the  two  forms  of  the  ba- 
cillus forming  acid  on  lactose.  In  order  then  to  complete  our  state- 
ment of  this  group  of  organisms  including  the  still  doubtful  bacilli 
which  act  on  lactose  the  following  series  is  required : 

(1)  "Shiga"  type:  attacks  glucose;  without  action  on  other  sugars 
including  mannite  and  lactose. 

(2)  "Flexner-Harris"  type:  attacks  glucose,  mannite  and  dextrine; 
does  not  attack  lactose. 


132  Simon  Flexner. 

(3)  "Bacillus  Y" :  attacks  glucose  and  mannitc;  no  action  on  dex- 
trine and  lactose. 

(4)  Duval  and  Shorer  "Bacillus  A":  attacks  glucose,  mannite  and 
lactose ;  no  action  on  dextrine. 

(5)  Duval  and  Shorer  "Bacillus  B" :  attacks  glucose,  mannite,  dex- 
trine and  lactose. 

The  manner  in  which  this  group  of  organisms  agrees  and  differs  is 
of  interest  and  importance,  and  cannot  fail  to  arouse  the  suspicion 
that  their  physiological  properties  are,  at  present,  in  a  very  unstable 
condition.  We  are  therefore  warned,  as  it  were,  away  from  any  at- 
tempt to  employ  the  physiological  activities  alone  as  bases  of  sub- 
divisions of  the  entire  family — if  family  it  be — of  the  dysentery  bacilli. 
And  it  is  self-evident  that  the  future  study  of  the  bacilli  of  the  Shiga 
class — so-called — must  be  conducted  with  greater  delicacy  and  pre- 
cision than  in  the  past  in  order  that  the  extent  of  the  variations  which 
the  class  presents  may  be  ascertained  with  accuracy. 

Besides  the  last  considered  bacilli  which  have  a  strong  resemblance 
to  the  bacillus  of  dysentery,  Wollstein  and  Dewey,  Kendall,  and  Duval 
and  Shorer  have  encountered  another  bacillus  which  agrees  with  that 
organism  in  some  qualities  but  which  is  probably  entirely  distinct  from 
it.  The  chief  cultural  peculiarity  of  this  unidentified  bacillus  is  its 
strong  alkali  formation  in  litmus-milk.  Duval  and  Shorer  give  the 
fullest  description  of  the  organism  from  which  the  following  is  ab- 
stracted:- The  bacillus  possesses  morphological  and  staining  properties 
which  do  not  distinguish  it  from  the  "Shiga"  type  of  B.  dysenteriae. 
In  cultures  upon  the  ordinary  fluid  and  solid  nutrient  media  it  is  also 
indistinguishable.  The  agglutinations  with  horses'  anti-dysenteric 
serum  is  positive  up  to  1  1500  to  1  :iooo.  On  the  other  hand,  litmus- 
milk  and  semi-solid  jelly  (Hiss)  serve  to  bring  out  striking  differences. 
The  former  shows  a  primary  acidity,  after  which  an  amphoteric  and 
then  alkaline  reaction  appears.  But  the  last  instead  of  remaining 
moderate  goes  on  to  strong  alkalinity,  the  milk  assuming  at  times  a 
blue-black  color.  With  some  of  the  early  isolations  the  milk  underwent 
peptonization ;  but  this  proteolytic  power  the  bacillus  loses  in  subcul- 
tures. The  semi-solid  jelly  often  establishes  rapidly  a  distinction  in 
that  a  part  of  the  bacilli  of  this  kind  are  sufficiently  motile  to  cloud 
the  medium.  But  as  a  certain  number  of  the  cultures  are  either  non- 
motile  or  very  feebly  motile,  the  milk  medium  must  be  resorted  to  for 
differentiation — a  process  requiring  some  days.  As  these  bacilli  do  not 
attack  the  sugars,  except  dextrose,  the  serum-water  medium  is  not 
useful    for    purposes    of    differentiation    (distinction    from    B.    fecalis 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  133 

alkaligenes).  Two  rabbits  were  immunized  to  cultures  of  the  '"al- 
kaline" bacilli.  The  serum  of  these  animals  was  positively  agglutina- 
tive 1 :20,ooo  with  the  bacilli  used  for  inoculation  and  1  -.25  to  1  150  with 
dysentery  bacilli.  The  exact  position  of  this  organism  is  left  unes- 
tablished,  but  it  probably  is  entirely  distinct  from  the  group  of  B. 
dysenteriae. 

One  of  the  immediately  suggestive  facts  brought  out  by  the  tables 
in  the  foregoing  reports  is  the  great  variation  in  numbers  of  dysen- 
tery bacilli  isolated  from  the  cases.  When  one  glances  through  the 
tables  and  observes  examples  yielding  1,  2,  3  or  a  half-dozen  colonies 
of  the  bacillus  he  must  be  impressed  with  the  narrow  line  which  sepa- 
rates "positive"  from  'negative"  examinations ;  besides  which  he  may 
be  led  to  wonder  whether  an  organism  which  occurs  in  such  small 
numbers  as  these  figures  indicate  can  have  any  specific  relation  to 
pathological  states  of  the  intestine.  The  latter  question  has  already 
been  referred  to  in  this  discussion,  but  it  is  desirable  to  add  a  word 
upon  the  former  one. 

In  the  course  of  the  summer's  work  I  became  convinced  that  the 
isolation  of  the  dysentery  bacillus  from  difficult  stools  was  often  de- 
termined by  incessant  vigilance  and  the  transplantation  of  very 
large  numbers  of  colonies  to  glucose-agar  or  the  semi-solid  jelly.  Since 
the  colony-form  is  only  roughly  useful  in  selecting  favorable  colonies 
it  becomes  essential  to  transfer  to  one  of  these  media  every  suspicious 
colony  arising  on  the  plates ;  and  thus  several  score  of  failures  may 
at  last  be  crowned  with  one  or  more  successful  tubes.  It  is  unnecessary 
to  add  that  even  this  costly  method  does  not  serve  entirely  to  avert 
failure. 

On  the  other  hand,  the  statement  of  the  recovery  of  larger  numbers 
of  colonies — 30,  50,  etc. — does  not  indicate  tbe  entire  or  even  relative 
richness  of  the  plates  in  dysentery  bacilli,  for  this  number  may  have 
been  obtained  in  one  or  two  pickings  from  a  few  plates,  after  which 
no  further  search  was  made.  That  the  bacillus  may  occur  in  much  larger 
numbers  and  even  exceed  the  other  intestinal  bacteria  is  shown  by  those 
cases  (reported  by  Duval  and  Shorer)  in  which  the  dysentery  bacilli 
were  present  either  alone  or  in  such  overwhelming  numbers  as  to  sup- 
press entirely  the  growth  of  the  colon  bacilli. 

I  have  entered  into  a  consideration  of  the  facts  of  the  numerical  re- 
lation of  the  bacilli  to  show  that  I  have  not  overlooked  their  bearing 
upon  the  pathogenic  properties  of  the  organism  and  to  emphasize,  more 
especially,  tbe  imperfection  in  our  methods  of  isolating  the  bacillus 
from  dejecta.     For  it  is,  I  think,  highly  probable  that  only  rarely  and 


134  Simon  Flexner. 

under  unusual  circumstances  are  the  conditions  so  favorable  as  to  yield 
to  our  present  methods  the  organisms  in  large  numbers.  And  hence 
the  prediction  can  be  ventured  that  some  other  procedure,  possibly  one 
of  enrichment  analogous  to  that  used  in  isolating  the  comma  bacillus 
from  choleraic  discharges,  will  yield  far  more  constant  and  unam- 
biguous results.  Indeed,  Shiga  having  appreciated,  apparetnly,  this 
difficulty  has  devised  a  method  of  enrichment,  but  unfortunately  it  is 
too  complex  and  initially  difficult,  in  its  present  form,  for  application  to 
routine  work. 

It  is  perhaps  unfortunate  that  more  attention  was  not  paid  to  the 
agglutination  of  the  dysentery  bacilli  and  possibly  other  bacteria  grow- 
ing upon  the  plates  by  the  blood  of  the  patients.  The  concentration  of 
the  work  into  the  few  hot  summer  weeks,  during  which  the  great  ma- 
jority of  the  cases  arise,  and  the.  detailed  nature  of  the  cultural  studies 
rendered  the  systematic  investigation  of  the  agglutination-value  of  the 
blood  impractical.  Besides  this,  it  was  soon  discovered  that  to  obtain 
even  the  small  quantity  of  blood  needed  for  the  test  so  prejudiced  the 
mothers  in  dispensary  and  tenement-district  practice  that  they  became 
obstinate  and  often  declined  treatment.  The  circumstances  were  dif- 
ferent in  hospital  practice  and  consequently  Bassett's  records,  which 
are  based  upon  fuller  studies  by  Winne,  and  Wollstein's  and  Dewey's 
and  Cordes'  results  are  of  reliability  and  value.  It  is  to  be  hoped  that 
Dr.  Winne  will  publish  his  figures  in  detail ;  but  the  data  given  in  the  sev- 
eral reports  exhibit  the  high  degree  of  agglutinability  which  may  be 
acquired  by  the  blood,  as  well  as  the  uncertainty  of  the  agglutination- 
test  as  an  index  of  the  presence  of  B.  clysenteriae  in  the  intestine  or 
discharges.  The  original  studies  on  agglutination  made  by  Duval  and 
Bassett  and  the  subsequent  ones  made  by  Wollstein  are  borne  out  by 
these  later  results.  That  the  reaction  may  persist  in  the  blood  for  some 
weeks  after  health  has  been  re-established  is  shown  by  several  in- 
tances  given  in  Bassett's  report. 

Conclusions. 

i.  The  Bacillus  dysenteriae  can  be  isolated  from  the  intestinal  dis- 
charges and  the  intestinal  mucosa  of  a  large  percentage  of  children 
suffering  from  the  diarrheal  diseases .  prevailing  along  the  Atlantic 
sea-board  of  the  United  States  during  the  summer  months. 

2.  The  Bacillus  dysenteriae  is  to  be  sought  especially  in  the  mucus 
thrown  off  by  the  intestinal  mucosa  in  these  diseases  and  in  the  sub- 
stance of  the  mucous  membrane  itself.     The  bacillus  exists  in  smaller 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  135 

numbers  in,  or  is  recovered  with  far  greater  difficulty  from,  the  fecal 
matter  that  often  is  admixed  with  the  mucus. 

3.  Blood  admixture  makes  the  isolation  of  the  bacillus  of  dysentery 
from  the  intestinal  discharges  more  readily  accomplished,  as  it  gen- 
erally indicates  infections  of  severer  grade ;  but  the  mere  presence  of 
blood  is  of  less  moment  than  the  occurrence  of  mucus,  since  it  is  in 
the  latter  material  that  the  bacillus  of  dysentery  resides. 

4.  The  number  of  colonies  of  Bacillus  dysenteriae  recoverable  in  cul- 
tures is  in  a  general  way  indicative  of  the  severity  of  the  lesions  and 
symptoms  of  the  disease.  Some  cases,  however,  of  marked  severity 
yield  few  colonies  and  others  of  marked  mildness  a  larger  number  of 
colonies  of  the  bacillus. 

5.  The  total  number  of  colonies  of  Bacillus  dysenteriae  obtainable 
is,  as  a  rule,  far  below  the  number  of  colonies  of  the  usual  intestinal 
bacteria  which  develop  upon  the  plates ;  but  in  a  very  few  instances 
the  number  of  colonies  of  the  dysentery  bacillus  equals  or  exceeds  that 
of  all  other  organisms,  and  in  exceptional  specimens  the  bacillus  alone 
appears  in  the  cultures. 

6.  The  type  of  Bacillus  dysenteriae  which  preponderated  in  the 
children  is  the  so-called  "Flexner-Harris"  organism.  The  "Shiga" 
type  of  the  organism  is  exceptionally  met  with,  and  occasionally  both 
types  are  found  in  association. 

7.  Types  of  Bacillus  dysenteriae  of  less  well-established  properties 
have  also  been  encountered.  Among  these  are  Bacillus  "Y"  of  Hiss 
and  Russell  and  another  distinct  type  which  demands  additional  study 
before  admission  to  the  group,  whose  special  property  is  its  power  to 
act  upon  lactose  with  acid  production. 

8.  The  blood  of  the  children  suffering  from  diarrheal  disease  ag- 
glutinates at  times  the  bacillus  of  dysentery  in  high  dilutions ;  but  this 
agglutination  by  the  blood  does  not  proceed  hand  in  hand  with  the 
occurrence  of  the  bacillus  in  the  intestine.  The  agglutination  reaction 
is  not  to  be  treated  as  an  index  of  the  presence  of,  or  infection  with, 
Bacillus  dysenteriae. 

9.  The  close  association  of  Bacillus  dysenteriae  with  the  intestinal 
mucosa,  and  the  increased  numbers  of  the  organism  found  under  defi- 
nite pathological  conditions,  the  established  pathogenic  action  of  the 
bacillus  for  human  beings,  and  the  specific  blood  changes  met  with  in 
many  of  the  cases  of  diarrheal  disease,  all  speak  for  a  relationship  of 
cause  and  effect  between  the  bacillus  of  dysentery  and  the  lesions  of 
the  intestine. 

10.  It  is  probable  although  it  is  not  proven  that  Bacillus  dysenteriae 


136  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

appears,  at  times,  among  the  saprophytic  bacteria  of  the  contents  of 
the  intestine.  The  frequency  of  its  isolation  in  all  grades  of  diarrheal 
disease  in  children  would  be  in  conformity  with  the  view  of  such  a 
saprophytic  existence  and  the  acquisition,  under  pathological  conditions, 
of  pathogenic  and  invasive  properties. 

n.  Should  it  be  established  that  Bacillus  dysenteriae  is  occasionally 
or  regularly  to  be  found  among  the  bacteria  of  the  cavity  of  the  intes- 
tine, the  dangers  of  the  entrance  from  without  of  specially  pathogenic 
examples  of  the  organism  are  not  to  be  disregarded.  The  contagious- 
ness of  bacillary  dysentery  among  adults,  and  the  rarer  instances  of 
diarrheal  contagion  among  children,  prove  the  necessity  of  recognizing 
such  an  extra-infectious  origin  of  the  disease. 

12.  Streptococci  in  large  numbers  are  found  frequently  associated 
in  cultures  with  Bacillus  dysenteriae.  Both  organisms  survive  side  by 
side  and  would  seem  not  mutually  to  inhibit  each  other's  development. 
What  part  is  to  be  ascribed  to  each  in  the  production  of  the  lesions  of 
the  intestine  and  the  symptoms  of  disease  is  not  established  by  this  in- 
vestigation. Xor  is  the  possible  action  of  any  other  of  the  many  bac- 
teria of  the  discharges  excluded  by  the  special  findings  of  the  investi- 
gation. 

13.  The  central  fact  brought  out  by  this  collective  investigation  is  the 
frequent  occurrence  in  the  diarrheal  diseases  of  children  of  a  specific 
micro-organism,  which  hitherto  has  been  held  to  be  of  special  pathogenic 
action  in  human  beings,  and  to  be  the  cause  of  that  form  of  dysentery 
among  adults  and  also  among  children,  which  is  characterized  by 
necrotic  and  pseudo-membranous  lesions  of  the  intestine  and  marked 
infectiousness. 

14.  The  lesions  of  the  intestines  observed  in  the  children  who  have 
succumbed  to  the  diarrheal  diseases  treated  of  in  this  publication  have 
been  very  varied  in  character ;  but  there  has  rarely  been  found  among 
them  the  particular  kinds  of  pathological  changes  which  characterize 
pseudo-membranous  entero-colitis. 


A  CLINICAL   STUDY   OF    SIXTY-TWO    CASES    OF   INTES- 
TINAL INFECTION  WITH  THE  BACILLUS  DYSENTERIC 
(SHIGA)  IN    INFANTS. 

BY 

LINNAEUS  EDFORD  LA  FETRA,  M.D., 

Instructor  in   Pediatrics,   Columbia  University;   Chief  of   Clinic,   Department   of 

Pediatrics,  Vanderbilt  Clinic;    Assistant  Visiting  Physician 

to  the  Babies'  Hospital. 

AND 

JOHN    HOWLAND,    M.D., 

Pathologist    to    the    New    York    Foundling    Hospital ;     Attending    Physician    to 

Wiliard   Parker  and  Riverside  Hospitals ;    Assistant  Attending 

Physician,  St.  Vincent's  Hospital. 

The  cases  that  make  up  the  material  for  this  study  were  all  observed 
by  the  writers  at  the  Vanderbilt  Clinic  during  the  months  of  July, 
August  and  September,  1903.  The  patients  were  brought  to  the  dis- 
pensary, which  is  an  outpatient  service,  and  the  milder  cases  were  seen 
only  every  alternate  day.  The  severer  cases  were  in  addition  visited 
and  treated  at  their  homes  on  the  days  that  they  did  not  come  to  the 
clinic  by  Drs.  Peter  Irving  and  Frank  Erdwurm,  whose  efficient  co- 
operation made  full  reports  possible.  To  insure  uniform  records  use 
was  made  of  printed  blanks  upon  which  could  be  recorded  the  history, 
physical  examinations  and  daily  observations  of  each  case. 

When  a  child  was  brought  with  a  history  of  diarrhea,  effort  was 
made  at  the  time  of  the  first  visit  to  obtain  a  fresh  stool  for  immediate 
bacteriological  examination.  By  using  the  thermometer  by  rectum 
or  inserting  a  suppository  it  was  possible  in  most  cases  to  obtain  a 
stool.  The  stool  was  passed  into  a  sterile  piece  of  unbleached  cotton, 
then  taken  at  once  to  the  bacteriologists,  Duval  and  Shorer,  work- 
ing in  the  same  building.  In  forty-eight  hours  a  bacteriological  report 
on  the  presence  or  absence  of  the  dysentery  bacillus  could  be  obtained. 

At  first  only  those  cases  were  examined  bacteriologically  that  gave 
the  history  or  presented  symptoms  of  a  moderately  severe  diarrhea ; 


138  Linnaeus  Ed  ford  La  Fetra  and  John  Howland. 

but  later,  on  account  of  the  numerous  positive  findings,  all  cases  of 
mild  diarrhea  and  intestinal  indigestion  were  also  examined. 

This  makes  our  report  of  far  greater  interest,  our  cases  being  succes- 
sive ones,  no  selection  at  all  having  been  attempted  after  the  first 
4  cases,  while  other  cases  that  have  been  published  up  to  this  time 
have  been  those  selected  for  their  severity  or  for  some  reason  regarded 
as  suitable  and  likely  to  contain  the  bacillus  of  dysentery.  One  small 
series  examined  seriatim  has  been  reported. 

Some  patients  were  seen  but  once ;  in  others,  though  seen  several 
times,  the  result  of  the  disease  was  unknown.  Undoubtedly  some  of 
these  cases  recovered  so  that  they  were  not  brought  back  to  the  clinic ; 
others  refused  to  return  after  the  first  injection  of  the  serum. 

As  routine  measures,  cow's  milk  was  immediately  discontinued  and 
not  resumed  for  several  days ;  in  breast-fed  infants  the  nursing  was 
forbidden  for  a  time.  Barley  water,  rice  water  or  broth  was  substi- 
tuted for  the  milk.  Free  catharsis  was  obtained  by  means  of  calomel 
and  castor  oil.    Other  drugs  were  rarely  used. 

There  were  in  all  62  cases  of  infection  with  the  Bacillus  dysenteric 
(Shiga);  of  these  2  were  observed  during  June,  33  in  July,  18  in 
August  and  9  in  September.  The  investigation  was  begun  late  in  June 
and  ended  September  15th,  so  that  only  during  July  and  August  were 
observations  carried  throughout  the  whole  of  the  month ;  hence  the 
small  number  of  cases  reported  in  the  first  and  last  months,  June  and 
September,  has  little  significance. 

Age. — Eight  of  the  patients  were  under  3  months;  14  were  between 

3  and  6  months ;  1 5  were  between  6  and  9  months ;  9  were  between  9 
and  12  months  and  15  were  over  one  year,  and  of  1  the  age  was  not 
stated. 

Of  the  8  patients  under  3  months  of  age,  5  were  only  slightly  sick, 
1  moderately  and  2  severely  sick. 

Of  the  14  patients  between  3  and  6  months  7  were  mild  infections; 

4  moderately  severe ;   2  severe,  and  1  patient  was  seen  only  once. 

Of  the  15  patients  between  6  and  9  months  3  were  mild  cases ;  9  were 
moderately  severe,  and  3  severe. 

Of  the  9  between  9  and  12  months  5  were  moderately  severe  and  4 
severe  cases. 

Of  the  15  over  12  months,  1  was  a  mild  case,  n  were  moderate 
cases  and  3  severe  cases. 

From  an  analysis  of  these  cases  it  would  appear  that  the  number 
of  moderately  severe  and  severe  cases  increases  proportionately  with 
the  increase  in  age.     This  is  explained,  however,  by  the  fact  that  a 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  139 

majority  of.  the  mild  cases  under  6  months  of  age  in  this  series  were 
breast-fed. 

Previous  Illness. — An  attempt  was  made  to  learn  if  the  patient  had 
previously  suffered  from  diarrhea  and  by  reason  of  this  was  more  sus- 
ceptible to  infection  with  the  Bacillus  dysentericc.  The  statements 
were  so  unreliable  that  no  conclusions  could  be  drawn.  No  other 
predisposing-  cause  in  the  way  of  disease  could  be  discovered. 

Character  of  Food. — Of  the  14  severe  cases,  1  was  breast-fed,  5  were 
given  condensed  milk,  2  Straus'  sterilized  milk,  2  grocer's  milk,  3  fairly 
clean  bottled  milk,  and  1  case  not  stated. 

There  were  14  children  entirely  breast-fed ;  2  children  were  partly 
breast-fed ;  1 1  children  had  been  fed  on  grocery  milk ;  7  on  bottled 
milk  of  fair  quality ;  8  were  fed  partly  or  wholly  on  sweetened  or  un- 
sweetened condensed  milk ;  5  on  proprietary  foods  without  milk ;  2 
on  Straus'  sterilized  milk ;  2  on  home  sterilized  milk ;  1  on  peptonized 
milk;  4  on  general  diet  and  no  statement  in  regard  to  7. 

Length  of  Symptoms  before  Observation  : 

Symptoms  had  existed  for     1  day in     5  cases 

"       2  days   in     7 

"       3      "      in     8 

"  "      4      "       in     5 

5-10   days   in  17 

"  "  "     11-14      "       in     7 

"       1-3   months    in  10 

No  statement    in     3 

Forty  of  the  cases  had  given  symptoms  for  one  week  or  less  show- 
ing that  they  were  brought  while  they  were  still  acutely  ill. 

Length  of  Time  under  Observation: 

1-3  days  28 

4-7  days  12 

8-14  days 10 

2  weeks  and  over 8 

No  record   (seen  only  once) 4 

Condition  at  the  Beginning  of  Attack. — Of  the  62  cases  whose  con- 
dition at  the  beginning  of  the  attack  was  noted,  31  were  well  nourished ; 
2  fairly  nourished;  11  poorly  nourished;  13  were  emaciated,  weak  and 
in  wretched  condition ;  2  were  in  collapse  and  practically  moribund  on 
the  first  examination. 

It  is  most  interesting  and  instructive  to  notice  in  this  connection 
that  of  the  31  children  who  were  well  nourished,  14  had  a  very  mild 
form  of  disease,   12  were  moderately   ill  and  only   5   severely  ill;  of 


140  Linnaeus  Ed  ford  La  Fetra  and  John  Hoivland. 

the  2  fairly  nourished,  i  was  very  slightly  and  the  other  severely  ill ; 
of  the  II  poorly  nourished,  7  were  moderately,  3  severely  and  only  1 
slightly  ill.  Of  the  13  emaciated,  3  were  severely  ill,  10  moderately 
and  not  one  had  the  disease  in  a  mild  form.  From  this  it  would  seem 
that  the  most  important  factor  in  determining  the  character  and 
severity  of  the  disease  is  the  previous  condition  of  the  child. 

Of  the  cases  observed  by  us  16  were  very  mild,  31  were  moderately 
severe  and  14  were  severe ;  1  case  was  lost  sight  of  and  so  was  un- 
classified. We  characterized  as  mild  those  cases  that  had  more  fre- 
quent passages  than  normal,  but  not  more  than  10  a  day,  with  a  tem- 
perature of  less  than  100.5  °  F-  These  stools  contained  undigested  food, 
usually  mucus  but  no  blood  (such  cases  were  not  really  sick).  Those 
cases  were  classified  as  moderate  that  had  a  temperature  over  100.50  F. 
or  had  frequent  passages  containing  mucus  and,  sometimes,  a  slight 
amount  of  blood.  These  cases  were  really  sick  and  showed  con- 
stitutional symptoms.  The  severe  cases  comprised  those  having 
marked  constitutional  symptoms  and  great  depression  with  frequent 
mucous  stools,  often  with  much  blood;  and,  while  the  temperature 
of  these  cases  was  usually  considerably  elevated,  many  of  them  and 
some  of  the  most  severe  ran  an  almost  afebrile  course. 

Thirty-four  cases  did  not  show  a  temperature  of  over  100.50  F. 
and  thus  more  than  one-half  of  those  seen  by  us  were  practically  with- 
out fever.  Vomiting  occurred  in  19  cases,  usually  at  the  beginning  of 
the  attack. 

The  number  of  stools  in  24  hours  was  from  2  to  5  in  5  cases 
"  "         "        "       "    "        "        "  "     5  to  10  in  35  cases 

"  "         "        "       "     "        "        "      over  10  in  20  cases. 

In  2  cases  not  stated. 

Two  cases  had  stools  without  any  mucus ;  mucus  was  present  in 
all  other  cases  in  varying  quantity  from  a  minute  amount  to  prac- 
tically the  whole  stool.  Blood  was  present  in  17  cases;  the  quantity 
of  blood  varied  from  a  few  streaks  to  enough  to  color  all  the  mucus ; 
no  clots  of  blood  were  ever  observed. 

The  following  cases  are  cited  as  representing  types  of  the  different 
degrees  of  severity : 

Mild.  (Breast-fed  infant)  P.  B.,  5  months  old,  nursed  entirely,  every  3 
hours.  Had  never  been  ill  and  his  condition  at  the  beginning  of  the  attack  was 
good.  His  illness  began  two  days  previously  with  3  green  mucous  stools  a  day. 
No  fever,  no  vomiting,  no  blood  in  the  stools.  Physical  examination  was  nega- 
tive. He  was  rather  restless  but  otherwise  seemed  perfectly  well  and  had  a 
temperature  of  only  ioo°  F.     The  stool  seen  at  the  dispensary  was  green,  mod- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  141 

erately  large,  semi-liquid  with  mucus,  no  blood.  Breast-feeding  was  ordered 
discontinued  and  barley  water  feedings  substituted ;  small  doses  of  calomel  were 
given.  The  following  day  the  condition  was  the  same,  character  of  stools  un- 
changed and  the  same  number.  The  third  day  the  stools  were  2  in  number, 
yellow,  fecal,  with  only  a  little  mucus  and  everything  seemed  so  satisfactory  that 
breast  feeding  was  resumed  with  an  absolutely  uninterrupted  convalescence. 

Such  a  case  would  formerly  have  been  considered  a  very  mild  case 
of  intestinal  indigestion ;  but  the  bacteriological  examination  showed 
the  presence  of  the  "Flexner-Harris"  or  acid  producing  type  of  dysen- 
tery organism. 

Mild.  (Bottle-fed  infant)  W.  P.,  6  months  old,  in  good  general  condition. 
Never  had  the  breast,  bottle-fed  from  birth  ;  at  onset  was  being  fed  a  mixture 
of  malted  milk  3  teaspoonfuls,  and  water  ,1  pint;  of  this  5  oz.  were  given  every 
2  or  3  hours.  Illness  began  3  days  previously  with  loose,  mucous  stools,  averag- 
ing 10  a  day.  no  blood,  no  vomiting.  Temperature  100.5°  F.  Did  not  seem  ill. 
Acid  type  of  organism  cultivated  from  stools.  Patient  was  under  observation  6 
days.  Child  was  given  calomel  and  shortly  after  a  dilute  milk  modification. 
After  treatment  was  begun  the  stools  were  never  more  than  4  a  day,  were  yellow 
and  fecal  but  had  mucus  and  a  few  curds.  These  disappeared  and  the  child  was 
discharged  entirely  well. 

Moderately  severe.  R.  W.,  5  months  old.  Was  nursed  for  4  months,  after- 
wards fed  on  3  parts  Straus'  milk  and  2  parts  barley  water,  taking  only  15  ounces 
of  the  mixture  in  24  hours.  The  baby  was  in  good  general  condition  when  taken 
sick  2  weeks  before  being  brought  to  the  clinic ;  the  onset  had  been  with  vomit- 
ing and  fever;  there  had  been  marked  loss  of  flesh  and  the  baby  was  markedly 
prostrated  when  first  seen.  The  stools  were  from  5  to  7  a  day,  large,  green  with 
considerable  mucus  and  some  blood.  Temperature  ioo°  to  ioi°  F.  The  ''Flex- 
ner-Harris" type  of  organism  was  cultivated  from  the  stools.  The  patient  was 
under  observation  9  days ;  was  given  calomel  and  the  milk  was  stopped  2  days ; 
then  a  weak  milk  modification  was  given.  The  stools  became  less  frequent,  their 
character  improved  and  on  the  last  day  seen  were  only  2  in  number,  yellow  and 
with  some  mucus.     The  temperature  was  normal. 

Severe.  M.  K.,  7  months  old.  Had  been  under  observation  for  6  months  at 
the  beginning  of  which  time  he  weighed  4  pounds  15  ounces.  Had  been  fed  on 
various  milk  modifications  and  had  gained  very  well ;  at  the  time  of  the  attack 
was  of  fair  weight  and  in  good  general  condition.  For  about  10  days  had  suf- 
fered from  symptoms  of  intestinal  indigestion.  The  stools  were  yellow,  frothy 
and  large  and  there  were  10  to  12  in  24  hours.  There  was  some  tenesmus  and 
mucus  in  great  amount,  no  blood.  Free  catharsis  and  the  substitution  of  barley 
water  for  the  milk  had  no  effect ;  stools  were  still  frequent  and  yellow  and  once 
contained  a  little  blood.  The  true  Shiga  type  of  organism  was  found  by  culture 
from  the  stools.  The  temperature  was  always  low  never  going  above  100.40  F. 
Imperial  Granum  was  no  better  borne  than  the  barley.  The  child  constantly 
failed  and  the  stools  were  still  frequent,  as  many  as  16  in  a  day;  bismuth  only 
colored  the  stools.  In  a  week  the  child  was  in  desperate  straits,  eyes  sunken, 
fontanel  depressed  and  pulse  imperceptible.  He  was  given  20  c.c.  of  "Shiga" 
serum  in  the  buttocks  on  2  successive  days.     Stimulation  by  whiskey  and  strych- 


142  Linnaeus  Ed  ford  La  Fetra  and  John  Howland, 

nine  and  hot  baths  was  rescrted  to.  Child  was  also  given  a  milk  and  water  mix- 
ture i  to  6.  Very  decided  improvement  was  seen  almost  immediately,  the  num- 
ber of  stools  diminishing  in  one  day  from  16  to  4;  this  was  3  days  after  the  first 
injection  of  serum.  From  this  time  convalescence  was  rapid  and  3  months  after 
the  attack  he  was  a  fat,  well-nourished  child,  taking  milk  well  and  digesting  it. 

Fatal  Cases.- — To  cur  knowledge  there  were  4  fatal  cases.  It  is 
possible  that  some  others  of  the  eases  observed  died  but  not  while 
under  observation,  nor  were  any  in  a  moribund  condition  when  last 
seen. 

(1)  J.  C.j  10  months  old,  in  poor  condition  and  emaciated;  living  in  a  tene- 
ment in  fair  surroundings  but  badly  cared  for ;  was  taken  with  diarrhea  while 
being  fed  a  weak  barley  water  and  milk  mixture.  No  history  of  previous  illness, 
and  he  had  been  bottle  fed  for  8  months.  The  onset  was  without  vomiting  but 
with  moderate  fever  and  with  frequent  mucous  stools,  8  a  day,  no  blood.  When 
first  seen  on  the  second  day  of  the  attack  the  baby  was  markedly  anemic,  fontanel 
depressed,  heart  very  feeble ;  circulation  poor ;  extremities  cold ;  no  distention. 
Lungs  negative.  Very  restless.  Milk  stopped  and  barley  water  given  and  white 
of  egg  with  whiskey.  Temperature  101.80  F.  Stools  were  small  and  green  muco- 
purulent, with  streaks  of  blood.  Following  day  child  was  extremely  prostrated; 
temperature  1010  F. ;  edema  of  face  and  lower  extremities;  respiration  shallow, 
radial  pulse  imperceptible.     Death  36  hours  later. 

True  Shiga  type  of  the  dysentery  organism  was  separated  from  the  stools  on 
the  first  day  of  observation. 

(2)  G.  EL,  10  months  old,  in  fair  condition,  living  in  a  filthy  tenement,  with 
little  sunlight  and  poor  care  ;  was  taken  sick  while  being  fed  a  condensed  milk 
mixture.  He  had  been  nursed  until  3  months  old.  The  onset  was  acute  by 
vomiting,  high  fever,  103. 50  F.,  and  diarrhea;  stools  were  6  to  7  a  day  and  con- 
tained mucus,  no  blood.  When  first  seen,  4  days  after  the  beginning  of  the  at- 
tack, the  child  was  somewhat  emaciated ;  fontanel  not  sunken ;  temperature 
103  °  F. ;  very  restless  and  with  some  tenesmus.  Put  on  barley  water  and  fol- 
lowing catharsis  was  given  a  bismuth  mixture.  On  the  seventh  day  of  the  at- 
tack was  given  10  c.c.  of  "Harris"'  serum,  and  these  injections  were  repeated  on 
the  eighth  and  ninth  days.  By  the  fourteenth  day  the  general  condition  was 
somewhat  improved,  the  temperature  having  fallen  to  ioo°  F.,  pulse  still  rapid. 
The  diarrhea  had  much  diminished  so  that  there  were  only  2  or  3  yellow  fecal 
stools  a  day.  A  weak  milk  mixture  was  given  with  no  bad  effect  upon  the  in- 
testinal condition,  but  the  child  gradually  failed,  and  in  spite  of  stimulation  by 
whiskey  and  strychnia  the  extremities  became  cold,  edema  came  on  and  the  heart 
gradually  gave  out  4  weeks  after  the  beginning  of  his  attack.  The  mother  was 
densely  ignorant  and  failed  to  carry  out  directions,  especially  in  regard  to  feed- 
ing; moreover  she  refused  to  have  the  child  admitted  to  a  hospital.  The  "Flex- 
ner-Harris"  type  of  organism  was  separated  from  the  stools  on  the  first  day  of 
observation. 

(3)  A.  K.,  3  months  old,  fairly  nourished,  living  in  a  clean  tenement  but  with 
little  care.  Had  been  nursed  entirely  for  one  month.  Was  taken  sick  while 
being  fed  on  Straus'  sterilized  milk.  The  onset  was  sudden  with  fever  and  diar- 
rhea, no  vomiting.     Stools  were  mucous  but  contained  no  blood,  12  a  day;    there 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  143 

was  much  tenesmus.  First  seen  7  days  after  the  beginning  of  the  attack;  the 
child  was  anemic  and  in  collapse.  Fontanel  depressed.  Heart  normal ;  lungs — 
fine  rales  at  both  bases  behind.  Child  was  admitted  to  the  Babies'  Hospital  4 
days  later  and  was  given,  along  with  other  treatment,  10  c.c.  of  "Harris"  serum. 
Refused  food  and  later  regurgitated  after  feeding.  Temperature  remained  be- 
tween 1030  and  105°  F.  and  the  child  died  48  hours  later.  The  stools  had  dimin- 
ished to  4  a  day. 

The  "Flexner-Harris"  type  of  organism  was  separated  from  the  stools  on  the 
first    day    of    observation. 

(4)  M.  McK.,  7  weeks  old,  a  poorly  nourished  child,  living  in  a  dirty  tene- 
ment with  very  poor  care.  Was  taken  sick  with  diarrhea  while  being  fed  on 
condensed  milk  and  Eskay's  food.  The  baby  had  been  nursed  for  3  weeks,  but 
nursing  had  then  been  stopped  because  the  mother  developed  an  abscess  of  the 
breast.  The  onset  was  acute  with  vomiting  but  no  fever.  The  stools  were  5  to 
7  in  24  hours,  green,  mucous  and  offensive,  but  contained  no  blood.  When  first 
seen,  7  days  after  the  beginning  of  the  attack,  the  child  was  much  prostrated 
and  anemic,  temperature  ioo°  F.  and  pulse  100  and  weak,  cold  extremities  and 
restless.  After  catharsis  was  fed  on  barley  water,  stools  remained  the  same ; 
refused  food  and  in  spite  of  stimulation  and  10  c.c.  of  "Harris"  serum  the  baby 
died  4  days  later  after  having  been  in  collapse  for  24  hours. 

Of  the  fatal  cases  all  were  under  one  year  of  age ;  were  artificially 
fed  and  were  in  very  poor  condition  when  first  observed,  and  also 
they  had  only  the  poorest  care  and  attention. 

Breast-fed  Cases. — There  wen;  14  infants  exclusively  breast-fed  that 
suffered  from  infection  with  the  Bacillus  dysenterixe. 

(1)  L.  P.,  6  weeks  old,  good  general  condition.  Stools  4  to  8,  watery,  with 
slight  amount  of  mucus,  no  blood.  Five  days  after  the  beginning  of  the  attack 
cathartics  given  and  substitution  of  barley  water  for  nursing;  in  24  hours  stools 
became  fecal  and  the  mucus  disappeared.  Never  any  vomiting  or  fever.  The 
"Flexner-Harris"  type  of  organism  was  isolated. 

(2)  F.  A.,  6  weeks  old,  good  general  condition.  Diarrhea  and  vomiting. 
Stools  soft  and  yellow  with  some  mucus,  7  in  24  hours.  Seen  only  once.  The 
"Flexner-Harris"  type  of  organism  was  isolated. 

(3)  P.  B.,  5  months  old,  good  general  condition.  Onset  without  vomiting 
or  fever.  Three  green,  mucous  stools  daily.  After  calomel  and  withholding  the 
breast  the  stools  became  yellow  and  fecal,  2  a  day,  and  on  the  third  day  of  treat- 
ment and  the  fifth  of  the  disease  the  child  was  discharged  perfectly  well.  The 
"Flexner-Harris"  type  of  organism  separated  from  the  stools. 

(4)  C.  F.,  2^2  months  old,  in  good  condition  at  the  beginning  of  the  attack. 
Onset  with  high  fever,  very  frequent,  green,  fluid  stools  with  curds  and  much 
mucus,  no  blood,  15  a  day.  Temperature  1040  F.  The  "Flexner-Harris"  type 
of  organism  found.     Referred  to  hospital  but  did  not  go.     Seen  only  once. 

(5)  D.  M.,  4  months  old,  in  good  general  condition;  3  to  5  green  and  mucous 
stools,  no  blood ;  diarrhea  began  2  days  before  coming  under  observation.  No 
vomiting  or  fever;  child  not  at  all  sick  but  the  stools  contained  a  little  undi- 
gested milk  and  were  green  for  4  or  5  days.  On  the  fourth  and  fifth  days  of 
treatment  10  c.c.  of  "Shiga"  serum  injected.     Two  days  after  this  the  stools  be- 


144  Linnaeus  Edford  La  Fctra  and  John  Howland. 

came   yellow   and   fecal   and   the   breast   feeding,   temporarily   withheld,   was    re- 
sumed.    The  true  Shiga  bacilli  were  found  in  the  stools. 

(6)  N.  H.,  8  weeks  old,  good  general  condition.  Diarrhea  with  6  to  8  fluid, 
mucous  stools  had  begun  2  days  before  coming  under  observation.  Xo  fever  or 
vomiting.  Castor  oil  and  barley  water  were  followed  by  prompt  recovery  in  2 
days.     The  "Flexner-Harris"  type  of  organism  was  found. 

(7)  W.  R.,  8  weeks  old,  in  good  general  condition.  Diarrhea  with  fluid, 
mucous  stools  began  without  fever  or  vomiting  2  days  before  coming  under  ob- 
servation. The  exhibition  of  castor  oil  and  barley  water  was  followed  by  re- 
covery on  the  fifth  day  of  the  attack.     True  Shiga  organisms  found  in  the  stools. 

(8)  C.  J.,  3  months  old,  in  good  general  condition.  Diarrhea  began  without 
fever  or  vomiting,  3  days  before  coining  under  observation ;  stools  8  to  io  fluid 
and  mucous,  no  blood.  Castor  oil  and  barley  water  effected  a  rapid  cure  in  2 
days.     The  "Flexner-Harris"  type  of  organism  was  isolated. 

(9)  L.  G.,  13  months  old,  fair  general  condition.  Onset  acute  with  fever  1 
week  before  coming  under  observation,  no  vomiting.  Stools  had  been  6  to  8  a 
day  fluid  and  mucous,  no  blood,  and  child  had  lost  much  weight.  Temperature 
101.80  F.  Calomel  and  barley  water  given.  Case  seen  only  once.  The  "Flexner- 
Harris"  type  of  organism  was  isolated. 

(  ic )  J.  D.,  1  year  old,  good  general  condition.  The  attack  of  diarrhea  began 
with  vomiting  and  fever ;  stools  4  to  9  in  24  hours,  loose,  mucous,  with  slight 
amount  of  blood.  When  seen  1  week  after  beginning  of  attack  temperature  was 
ioi°  F.  Child  was  somewhat  prostrated  and  emaciated.  Tenesmus  and  prolapse 
of  rectum.  Under  treatment  by  castor  oil  and  bismuth,  the  child  improved 
rapidly. 

(11)  L.  A.,  10  weeks  old,  excellent  general  condition,  had  been  sick  for  one 
week  with  diarrhea,  5  to  6  yellow,  slightly  mucous  stools  daily;  no  blood,  no 
fever,  no  vomiting.  Calomel  and  barley  water  effected  a  cure  in  2  days,  the 
stools  being  normal  in  24  hours.  The  true  Shiga  and  the  "Flexner-Harris"'  type 
of  organism  were  both  present. 

(12)  R.  A..  5  months  old,  good  general  condition.  Diarrhea,  6  to  8  fluid 
mucous  stools,  without  blood.  No  vomiting  or  fever.  Came  under  observation 
on  the  third  day  of  the  attack.  The  giving  of  calomel,  barley  water  and  bismuth 
mixture  for  two  days,  followed  by  a  gradual  resumption  of  nursing  effected  a 
cure  on  the  fifth  day.     The  true  Shiga  type  of  organism  was  present. 

(  13)  K.  M.,  8  months  old,  good  general  condition.  Diarrhea  without  vomit- 
ing or  fever.  Stools  fluid,  mucous,  no  blood,  8  to  10  in  24  hours.  Child  sick  3 
days  before  coming  under  observation ;  then  calomel,  bismuth  mixture  and  bar- 
ley water  brought  about  a  rapid  recovery. 

(14)  C.  S.,  7  months  old,  excellent  condition.  Diarrhea  with  8  or  9  fluid, 
very  mucous  stools  without  blood.  On  the  eighth  day  of  illness  the  child  was 
brought  to  the  clinic.  Calomel  and  bismuth  with  barley  water  were  followed  by 
the  reduction  of  stools  to  3  in  24  hours  and  by  the  change  in  character  to  normal. 

Of  the  breast-fed  cases  whose  records  are  complete  none  died,  all 
ran  a  very  mild  course,  the  average  being  3  to  4  days  after  coming 
under  observation.  Save  for  the  bacteriological  findings  these  was  noth- 
ing to  indicate  that  their  sickness,  had  anv  relation  to  true  dvsenterv. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  145 

These  casesr  morever,  with  hardly  an  exception,  were  in  well-nourished 
children.    Blood  was  observed  in  but  1  case. 

Type  of  Infection. — There  were  42  cases  in  which  the  "Flexner- 
Harris"  or  acid-producing  type  of  organism  was  found,  15  were  in- 
fected with  the  alkaline  or  true  Shiga  type ;  in  5  cases  both  types  of 
the  organism  were  found.  Of  the  42  acid  infections,  9  were  classi- 
fied as  mild  cases;  21  as  moderately  severe;  10  as  severe,  2  not  being 
classified.  Of  the  15  true  Shiga  infections,  5  were  mild;  6  moderately 
severe  and  4  severe.  Of  the  5  mixed  infections  1  was  mild  and  4 
moderately  severe. 

From  this  it  will  be  seen  that  in  the  acid  type  of  infection,  as  well 
as  in  the  true  Shiga  type,  the  moderately  severe  cases  were  most  nu- 
merous and  there  seemed  to  be  no  difference  in  the  severity  of  the 
disease  attributable  to  the  type  of  infection. 

We  did  not  use  at  all,  for  diagnosis,  the  agglutination  reaction  of 
the  blood  of  the  patients.  It  has  been  proven  in  children  as  well  as 
in  adults  that  this  reaction,  while  often  present,  is  uncertain  and  un- 
satisfactory for  the  reason  that  it  appears  late,  at  the  end  of  the  first 
week,  and  often  not  before  the  second  or  third  week  and  may  dis- 
appear early  in  the  prolonged  cases ;  so  that  we  can  make  our  diagnosis 
by  an  examination  of  the  stools  much  more  easily  and  more  satisfac- 
torily than  by  the  blood  of  the  patient. 

Treatment. — As  outlined  above  the  majority  of  the  cases  were  treated 
by  the  usual  methods  both  as  to  their  management  and  diet.  Milk, 
whether  breast  milk  or  cow's  milk  was  immediately  discontinued ; 
barley  water,  broth  or  some  proprietary  food  or,  rarely,  albumen  water 
being  given  in  its  place ;  it  was  only  resumed  when  the  acute  symptoms 
had  subsided.  Catharsis  by  calomel  and  castor  oil  was  the  invariable 
rule.  When  there  was  great  irritability  of  the  intestines  with  tenes- 
mus and  numerous  small  stools,  rectal  irrigations  without  or  with 
paregoric  were  employed.  For  temperature  that  gave  rise  to  nervous 
symptoms  irrigations  and  alcohol  sponging  were  resorted  to.  A  bis- 
muth mixture  was  used  in  a  few  cases. 

Serum  Therapy. — There  were  in  all  10  cases  in  which  the  serum  was 
injected:  4  were  infections  with  the  acid  type  of  organism  and  were 
given  "Harris"  serum ;  6  were  infections  with  true  Shiga  organism 
and  were  given  "Shiga"  serum.  Only  the  severe  cases  were  subjected 
to  this  treatment  as  it  was  found  that  in  dispensary  practice  the  mothers 
would  not  return  with  the  patients  after  injection  unless  the  disease 
was  apparently  serious. 

Of  the   injected  series,   cases    (1)    and    (2)    were  given    10  c.c.  of 


146  Linnaeus  Ed  ford  La  Fctra  and  John  Hozvland.  ■ 

"Harris"  serum  and  did  not  return  after  the  injections.  Case  (3) 
after  receiving  20  c.c.  of  "Harris"  serum  showed  decided  improvement ; 
after  the  injection  of  10  c.c.  additional  this  was  still  more,  marked  but 
the  child  died  of  marasmus  three  weeks  later  without  any  return  of  the 
diarrhea.  Case  (4)  was  already  improving  on  irrigations  before  the 
injection  of  the  serum  so  that  no  conclusions  can  be  drawn.  Case  (5) 
showed  decided  reduction  in  the  number  of  stools  and  improvement  in 
their  character  after  the  injection  of  10  c.c.  of  "Shiga"  serum  on  2  suc- 
cessive days.  Case  (6)  received  20  c.c.  of  "Shiga"  serum;  but  the  im- 
provement in  the  child's  condition  could  not  be  attributed  to  the  injec- 
tion. 

Case  (7)  received  10  c.c.  of  "Harris"  serum  when  moribund. 

Case  (8)  (the  severe  case  quoted  above)  improved  very  markedly 
after  2  injections  of  20  c.c  each  of  "Shiga"  serum,  but  only  after  an 
interval  of  3  days,  during  which  time  there  was  additional  stimulation 
and  change  of  diet,  so  that  the  effect  of  the  serum  is  doubtful. 

Cases  (9)  and  (10)  were  apparently  uninfluenced  by  the  injection 
of  "Shiga"  serum. 

A  rash  similar  to  that  seen  after  the  employment  of  diphtheria  anti- 
toxin was  observed  in  only  one  patient,  notwithstanding  the  fact  that 
the  quantity  of  serum  injected  was  very  much  greater  than  that  ordi- 
narily used  in  diphtheria. 

The  difficulties  of  administering  the  serum  in  outdoor  practice  must 
be  emphasized.  The  quantity  of  serum  of  the  present  strength  neces- 
sarily employed  is  large  and  must  often  be  injected  into  an  emaciated 
child,  producing  a  swelling  of  a  size  alarming  to  the  laity.  Objection 
also  arises  on  account  of  the  pain  of  the  injection. 

From  an  analysis  of  these  62  cases  observed  by  us,  it  seems  that  cer- 
tain points  are  worthy  of  special  note. 

( 1 )  The  unexpectedly  great  prevalence  of  the  dysentery  organism  in 
cases  of  diarrhea  in  infants,  at  least  during  the  summer  months.  Thus 
out  of  64  consecutive  cases  examined  in  the  Vanderbilt  Clinic  62  were 
positive. 

As  has  been  mentioned  before  this  is  the  first  large  series  of  cases 
examined  seriatim  that  has  been  made  and  the  result  is  certainly  strik- 
ing. It  is  all  the  more  so  when  we  consider  that  these  were  cases  in  dis- 
pensary practice  where,  with  the  severe,  the  very  mildest  cases  may  be 
seen.  Duval  and  Bassett  examined  25  successive  cases  and  found  the 
organism  in  19,  but  it  should  be  stated  that  the  patients  were  observed 
in  a  sanitorium  at  a  distance  from  Baltimore  where,  of  course,  only 
the  more  severe  cases  were  sent  from  the  dispensaries,  while  ours  were 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  147 

all  ambulant  patients  and  their  stools  were  examined  whenever  there 
was  the  slightest  sign  of  any  digestive  disturbance.  Our  cases  were 
also  seen  very  early  whereas,  in  hospitals,  the  cases  are  rarely  seen 
until  after  their  initial  symptoms  have  passed. 

(2)  All  types  of  diarrheal  disease,  as  characterized  by  their  clinical 
symptoms,  are  to  be  found  among  these  cases.  Some  were  examples  of 
severe  and  some  of  mild  ileo-colitis ;  others  could  only  be  classed  as  the 
mildest  form  of  intestinal  indigestion.  The  course  of  the  disease,  while 
usually  short,  was  prolonged  in  8  cases. 

(3)  As  compared  with  cases  of  summer  diarrhea  of  other  years  those 
in  this  series  were  in  general  much  milder  and  possibly  this  was  due 
to  two  factors:  (a)  The  cool  summer,  (b)  The  increasing  knowledge 
among  the  tenement  population  of  the  care  of  infants  and  their  food. 

(4)  The  striking  number  of  breast-fed  infants,  14  in  62  cases,  more 
than  20  per  cent,  of  all. 

In  the  series  of  Duval  and  Bassett  previously  mentioned  there  were 
4  breast-fed  cases  and  a  few  others  in  addition  have  been  reported. 
The  great  number  in  our  series  is  accounted  for  by  the  fact  that  all 
stools  from  patients  with  diarrhea  were  examined.  As  will  be  re- 
membered of  our  14  breast-fed  children  not  one  was  severely  or  even 
moderately  ill,  and  only  one  had  blood  in  the  stools.  Such  cases  would 
therefore  not  be  sent  to  hospitals  and  so  usually  their  stools  would  not 
be  available  for  examination. 

(5)  The  serum  treatment  was  not  given  in  a  sufficient  number  of 
cases  to  warrant  any  conclusions.  While  of  apparent  benefit  in  some 
cases  there  were  others  in  which  no  effect  whatever  was  noticed.  It 
may  be  that  larger  dosage  is  necessary;  but,  if  so,  the  serum  must  be 
more  concentrated  than  at  present. 


A  CLINICAL  STUDY  OF  THE  CASES  OF  DIARRHEA  PRO- 
DUCED     BY      BACILLUS      DYSENTERIC      (SHIGA), 
TREATED  DURING  THE  SUMMER  OF  1903  AT 
THE  THOMAS  WILSON  SANITARIUM.* 

BY  J.   H.   MASON  KNOX,  JR.,  PH.D.,  M.D., 
Physician  in   Charge,  Assistant  in   Pediatrics,  Johns   Hopkins   University. 

During  the  summer  of  1902  Duval  and  Bassett,  working  in  the 
laboratory  of  the  Thomas  Wilson  Sanitarium  under  a  grant  from  the 
Rockefeller  Institute  for  Medical  Research,  were  able  to  isolate  the 
Bacillus  dysenterise  (Shiga)  from  the  dejecta  of  forty-two  infants  suf- 
fering from  diarrheal  disorders.  Last  summer  the  work  was  con- 
tinued by  Bassett,  who  succeeded  in  finding  the  same  organism  in  the 
stools  of  upwards  of  forty  similar  cases.  His  report  appears  as  a 
separate  paper,  as  does  that  of  Winne,  late  assistant  resident  phy- 
sician at  the  Sanitarium,  which  gives  the  results  of  observations  made 
on  the  agglutination  reaction  of  the  dysentery  bacilli  isolated,  tested 
with  the  blood  of  these  patients  as  well  as  with  anti-dysenteric  serum. 

The  cases  were  not  examined  seriatim,  but  nearly  every  case  that 
had  a  history  of  acute  diarrhea,  as  well  as  those  whose  stools  contained 
mucus,  pus,  and  blood,  was  tested  bacteriologically. 

As  will  be  seen  later  the  majority  of  our  cases  were  severe  or  had 
persisted  a  long  time  before  coming  under  observation.  This  is  ac- 
counted for  by  the  fact  that  the  Sanitarium  is  at  some  distance  from 
the  city  and  the  mild  cases  and  those  responding  readily  to  treatment 
are  cared  for  in  the  dispensaries  of, the  city. 

This  report  will  be  confined  to  a  consideration  of  the  clinical  features 
presented  by  the  cases,  forty-three  in  number,  in  which  the  specific 
organism  was  demonstrated  in  the  stools. 

Previous  Attacks  of  Diarrhea. — There  was  but  a  single  instance 
among  our  cases  in  which  there  had  been  a  history  of  diarrhea  pre- 
vious to  the   one  from  which  the  patient  was  suffering  on  admission ; 

*The  Thomas  Wilson  Sanitarium  is  situated  in  the  country  ten  miles  from 
Baltimore,  where  each  summer  are  treated  from  300  to  400  infants  and  young 
children   suffering   from   gastro-intestinal   disorders. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


149 


i.e.,  the  children  were  brought  to  the  Sanitarium  during  their  first  ill- 
ness. Moreover,  there  was  no  history  of  any  one  in  the  household  other 
than  the  baby  suffering  from  diarrheal  disorders.  The  illness  of  the 
infant  was  the  first,  and  usually  the  only  case  of  intestinal  disease  in 
the  family — a  point  of  some  importance  in  considering  the  mode  of 
infection. 

Character  of  the  Food  and  Hygienic  Surroundings  at  Time  of  At- 
tack.— An  especial  effort  was  made  to  ascertain  the  nature  of  the  pre- 
vious surroundings  of  the  patient  and  the  character  of  his  diet.  In 
many  instances  reports  were  obtained  from  nurses  employed  by  the 
Sanitarium  who  visited  the  patients  in  their  homes.  These  factors 
have  been  gathered  together  in  the  accompanying  table.  It  should  be 
stated  that  our  patients  come  largely  from  the  middle  class  of  working 
people  of  Baltimore. 

FOOD    AND    HYGIENE. 


Total. 

Hygienic  Condition. 

Refrigera- 
tion. 

Water  with    or 
Between  Feedings. 

Food  at  Time  of  Illness. 

Good. 

Fair. 

Bad. 

Ice. 

No 
Ice. 

T3 

■5 

CQ 

"3 

a 
D 

■zo 

Breast,  exclusively 
Cow's   milk  (fair)  heated 
Cow's  milk  (fair)  raw 
Cow's  milk  (store)  heated 
Cow's  milk  (store)  raw 
Condensed  milk 
Table  diet 

2 
11 

6 
4 
5 
"4 

1 

0 

5 

1 
0 
0 

5 

1 

0 
5 
3 
2 

3 

5 
0 

2 

2 

2 
2 

4 
0 

0 

7 
1 
1 

0 

1 
0 

0 
2 
3 
3 

5 
6 
0 

0 

2 

O 
2 
O 

4 
0 

1 
7 
5 
2 

4 

10 

1 

I 

2 

I 
0 
I 
0 
0 

43 

12 

18 

13 

10 

19 

8 

30 

5 

The  milk  marked  "store"  in  the  preceding  table  was  bought  for 
the  babies  at  small  grocery  stores.  It  was  grossly  contaminated,  having 
a  bacterial  content  of  more  than  5,000,000  per  c.c.  The  milk  marked 
"fair"  was  delivered  at  the  homes  from  a  wagon  or  bought  at  a  dairy 
store.  It  contained  often  500,000  to  1,000,000  bacteria  to  the  c.c.  at 
time  of  delivery.  The  "heating"  mentioned  usually  meant  that  the  milk 
was  scalded  or  brought  to  a  boil  over  the  fire.  In  no  case  was  steam 
sterilization  or  Pasteurization  employed. 

Although  too  much  stress  should  not  be  laid  upon  the  tabulation  of 
a  short  series  of  cases  it  is  surprising  to  learn  that  the  quality  of  the 
milk  or  the  nature  of  the  child's  surroundings  seemed  to  make  little 


150  /.  H.  Mason  Knox,  Jr. 

difference  in  the  number  of  cases  admitted.  Moreover,  the  milk  given 
many  of  these  children,  though  fair,  was  never  of  the  first  quality. 
But  after  due  weight  is  attached  to  these  facts,  the  discrepancy  be- 
tween the  number  of  cases,  on  the  one  hand,  and  the  character  of  the 
food  and  the  hygienic  surroundings,  on  the  other,  makes  it  difficult 
to  charge  either  to  the  food  or  to  the  daily  care  of  the  infant  alone, 
this  outbreak  of  diarrheal  diseases  due  to  the  dysentery  bacillus. 

A  primary  infection  of  the  whole  milk  supply  of  the  community 
is  an  impossible  hypothesis,  as  our  patients  lived  in  widely  separated 
sections  of  the  city  and  obtained  their  milk  from  a  large  number  of 
remote  sources.  Moreover,  most  of  it  was  heated  before  using,  and 
many,  fed  exclusively  on  condensed  milk,  received  no  fresh  milk  at  all. 

Condition  of  the  Patient  Previous  to  Illness. — Very  rarely,  in  but 
two  instances,  was  there  definite  discoverable  cause  for  the  attack. 
The  diarrheal  disorder  was  usually  the  infant's  first  acute  illness.  How- 
ever, fully  25  out  of  the  43  cases  were  poorly  nourished  and  showed 
pronounced  stigmata  of  rickets,  while  10  were  markedly  emaciated. 
The  frequent  history  was  that  the  baby  for  some  weeks  or  months 
had  not  been  thriving  and  had  lost  in  weight,  when,  without  any  imme- 
diate cause  to  which  the  mother  could  attribute  it,  symptoms  indicative 
of  gastro-intestinal  disease  set  in. 

Length  of  Symptoms  Before  Observation. — The  series  of  cases  can 
be  divided  into  the  following  groups  with  reference  to  the  duration 
of  the  disease  before  observation : 

1- 10  days  10-20  days  More  than  20  days 

13  11  19 

But  one  case  was  seen  the  first  day  of  illness  and  only  four  before 
the  sixth  day. 

Length  of  Time  Under  Observation. — The  time  these  cases  were 
under  observation  varied  from  1  to  47  da}'s,  the  average  stay  at  the 
Sanitarium  for  the  whole  series  being  17  days.  The  more  protracted 
cases  occurred,  as  a  rule,  late  in  the  summer. 

The  Symptoms  of  the  Attack,  characterizing  the  cases  as  very  mild, 
moderate,  and  severe.  Our  experience  would  indicate  that  the  dysen- 
tery bacillus  in  the  infant's  intestinal  tract  may  produce  widely  differ- 
ent clinical  manifestations,  apparently  identical  with  the  various  forms 
of  the  familiar  so-called  "summer  diarrhea."  Our  cases  have  been 
roughly  divided  into  two  groups,  those  in  which  the  toxic  phenomena 
are  most  marked  and  those  in  which  there  is  evidence  of  serious  lesions 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


151 


of  the  intestinal  wall.     Each  of  these  divisions  may  be  mild,  moderate 
or  severe. 


Mild. 

Moderate. 

Severe. 

5 
0 

6 
8 

Ileocolitis 

14 

5 

14 

24 

Other  frequent  symptoms  are 


Vomiting 
Diarrhea. 
Fever. . . . 


Absent. 


(1) 
(4) 


Moderate. 


25     (2) 
17     (5) 


Severe. 


18     (3) 
26     (6) 


(1)  Less    than    4 

(2)  4-15 

(3)  More  than  15 


stools    in    24    hrs. 


(4)  Temperature  not  over  990 

(5)  between  990  and  ioi' 

(6)  higher  than  1010 


The  character  of  the  stools  is  thus  briefly  indicated 


None. 

Trace. 

Moderate. 

Much. 

Mucus 

0 

15 
10 

4 
10 
10 

30 
16 
15 

9 

Blood 

Pus 

8 

Complications  were  comparatively  rare.  Convulsions  occurred  as 
the  terminal  event  in  three  cases.  Broncho-pneumonia  was  recognized 
but  twice;  one  child  died  of  intestinal  obstruction,  and  one  developed 
pyemia.  In  six  instances  a  patient  was  readmitted  because  of  a  re- 
lapse of  the  disease  after  apparent  cure. 

Type  of  Organism. — In  all  our  cases,  as  is  brought  out  in  Bas- 
sett's  report,  only  the  so-called  "Flexner-Harris"  or  acid-producing 
type  of  the  organism  was  isolated;  that  is,  the  one  which  ferments 
mannite  with  acid  production. 


i52  J.  H.  Mason  Knox,  Jr. 

The  Results  in  our  series,  arranged  according  to  the  form  of  the 
infection,  are  as  follows : 


Well. 

Improved. 

Unimproved. 

Died. 

l   Mild 

3 
3 

2 

O 

3 

2 

2 
3 
5 

0 
1 
1 

0 
0 
0 

0 

0 

-    1 

Inflammatory        {    Mild 

0 

4 

13 

12 

1 

17 

Thus,  it  is  seen  that  of  a  total  mortality  of  17,  or  39  per  cent.,  the 
large  majority,  14,  occurred  in  the  cases  of  ileo-colitis,  most  of  which 
were  admitted  late  in  the  summer. 

It  is  well  known  that  many  of  these  cases  begin  with  simple  gastro- 
enteritis ;  and  the  difference  in  the  results  obtained  in  the  treatment 
of  the  two  forms  of  intestinal  disease  argues  strongly  the  importance 
of  prompt  abortive  measures. 

The  relation  of  the  previous  diet  to  the  results  is  thus  indicated : 


' 

Well. 

Improved. 

Unimproved. 

Died. 

Cow's  milk  of  all   kinds 

26 

14 

1 
2 

10 

1 
1 
1 

7 
5 
0 
0 

1 
0 
0 
0 

8 
8 
0 

1 

43 

13 

12 

1 

!7 

It  is  to  be  noted  that  of  the  14  cases  previously  fed  on  condensed 
milk,  8,  or  57  per  cent.,  died  at  the  Sanitarium  in  spite  of  treatment, 
and  but  one  really  recovered ;  while  of  the  26  cases  fed  on  cow's  milk 
at  their  homes,  8,  or  29  per  cent.,  died  and  10  were  permanently 
cured.  That  is,  that  although  the  condensed  milk  infants  are  per- 
haps less  liable  to  infection  with  the  dysentery  bacillus,  when  the  or- 
ganisms find  entrance  the  children  so  fed  have  less  resistance. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


l53 


a    • 
o  <u 

ox 
O  rt 
'5  -^ 

■3.2 

§Q 
u 

Unimproved. 

Well. 

Well. 

2 

"3 

Improved. 

Improved. 
Improved. 

Improved. 

Improved. 

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Result  of  Serum  Treatment. 

Favorable.  Fewer  stools. 
Brighter     ' 

Slightly  favorable.  Slow  re- 
covery 

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No  immediate  improvement 

Serum  of  doubtful  effect 
Action   of   serum,  if  any,  slow. 

Temperature  reduced 
Slow.     Doubtful 

Inert  or  slightly  helpful 

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Inert 
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Improvement  (?)  first,  inert  later 
Inert 

Inert.     (Broncho-pneumonia.) 
Inert 

General   Condition   of    Patient   at 
First    Injection. 

Acute  attack  at  sanitarium  in  ma- 
rantic infant 

Comatose  ;  irregular  pulse,  mucus 
and  blood  in  stools. 

Poorly  nourished,  collapsed.  Ex- 
tremities cold 

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Fair  condition.     Numerous   stools 

containing  mucus  and  blood 
Fair  condition 
Collapsed,  semi-comatose 

Poorly  nourished.     Muco-purulent 

stools,  with  blood 
Poorly  nourished,  feeble 

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Poorly  nourished.    Extremitiescold 
Collapsed,  semi-comatose 
Poorly  nourished.     Furunculosis 
Emaciated,  collapsed 
Collapsed,  drowsy 
Emaciated.         Marked      rickets. 

Drowsy 
Poorly  nourished 
Poorly  nourished 
Collapsed,  sunken  fontanel.   Many 

stools 

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154  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

Cases  Exclusively  Breast-fed. — Two  cases  only  occurred  in  this 
series : 

i.  Girl,  ten  weeks  old,  a  twin  (other  died  at  birth).  Family  very  poor  and 
care  wretched.  Child  had  never  been  well  nourished.  Illness  began  three  weeks 
before  admittance.  Stools  were  green,  six  to  seven  a  day,  with  mucus,  no  blood. 
Considerable  vomiting  and  colic. 

After  an  observation  of  two  weeks,  in  which  the  child  was  carefully  fed  and 
treated  according  to  the  ordinary  methods  without  serum,  she  was  discharged, 
improved. 

2.  Boy,  six  months  old.  Child  had  never  been  well  nourished,  always  sickly. 
Mother  weak  and  anemic,  living  in  poor  surroundings.  Child  nursed  very  irreg- 
ularly. Illness  began  three  weeks  before  admission,  with  diarrhea,  no  vomiting. 
Stools,  four  to  six  a  day,  containing  mucus,  no  blood. 

On  admission  the  child  was  markedly  emaciated,  with  pronounced  signs  of 
rachitis.    Temperature  varied  from  cj60-ioi°  F. 

Serum  was  given  without  effect,  and  at  the  end  of  two  weeks  the  child  died. 
This  was  apparently  a  terminal  infection  in  the  course  of  marasmus. 

Serum  Treatment. — Through  the  kindness  of  Dr.  Flexner  and  the 
generosity  of  the  Rockefeller  Institute  for  Medical  Research,  the  Sani- 
tarium was  supplied  with  antidysenteric  serum  obtained  from  horses 
immunized  against  both  types  of  the  organism. 

Because  of  the  distance  of  the  Sanitarium  from  Baltimore,  but  few 
early  cases  come  under  observation,  so  little  selection  could  be  made 
of  infants  favorable  for  this  treatment. 

Eliminating  a  number  of  instances  in  which  the  serum  was  given 
when  the.  patient  was  in  extremis  or  when  serious  complications  ob- 
scured its  action,  twenty  cases  remain  to  be  recorded.  The  preceding 
table  contains  the  more  important  data  with  reference  to  the  use  of  the 
serum. 

The  variety  of  the  serum  is  designated  by  the  letter  S  or  H,  indicat- 
ing serum  made  from  organisms  of  the  "Shiga"  or  "Harris"  type,  re- 
spectively. 

Cases  Treated  by  Serum  Injection. —  (Vide  table  on  page  153.) 

The  results  obtained  with  the  antidysenteric  serum  were  in  our 
hands  disappointing.  It  seemed,  however,  to  have  a  slightly  favor- 
able action  in  those  of  the  cases  in  which  it  was  employed  early  in 
the  disease,  particularly  in  the  first  case,  in  which  the  infection  took 
place  at  the  Sanitarium,  when,  in  a  markedly  emaciated  infant,  there 
was  definite  improvement  noticed  in  six  hours  following  the  injection 
of  the  serum;  in  the  great  majority  of  the  cases,  however,  it  seemed  to 
be  without  effect. 


A    CLINICAL    REPORT    OF    TWENTY-SIX    CASES    OF    IN- 
TESTINAL INFECTION  WITH  THE  BACILLUS 
DYSENTERIAE. 

BY   LOUISE  CORDES,   M.D., 
Pathologist  to  the  New  York  Infirmary  for  Women  and  Children. 

Two  of  the  twenty-six  cases  here  described  were  seen  in  the  wards 
of  the  Nursery  and  Child's  Hospital,  one  in  the  Babies'  Hospital  Dis- 
pensary, seven  in  the  wards  of  the  New  York  Infirmary  for  Women 
and  Children  and  sixteen  in  the  Out  Door  Department  of  the  same 
Institution. 

The  acid-producing  or  "Flexner-Harris"  type  of  the  Bacillus  dysen- 
teriae  was  found  in  twenty-five  cases,  the  true  Shiga  type  in  one. 

The  symptoms  of  the  infection  in  this  one  case  differed  in  no  way 
from  those  observed  in  the  twenty-five  others. 

Mild  as  well  as  severe  cases  of  intestinal  disturbances  were  studied. 

One  case  occurred  in  June,  thirteen  in  July,  ten  in  August  and  two  in 
September. 

Age  of  Patients. — Under  6  months,  4  ;  from  6  to  12  months,  5 ;  from 
12  to  18  months,  5 ;  from  18  months  to  2^  years,  10.  Two  cases  were 
in  children  aged  five  and  ten  years  respectively. 

Previous  Diarrhea. — A  history  of  previous  attacks  of  diarrhea  was 
obtained  in  6  cases;  in  17  no  previous  attack  had  occurred,  and  in  3 
no  trustworthy  history  of  previous  diarrhea  could  be  obtained. 

Condition  at  the  Beginning  of  the  Attack. — AVas  good  in  11;  fair  in 
4 ;  poor  in  9 ;  not  recorded  111  2. 

diameter  of  the  Food. — None  of  the  children  were  exclusively 
breast-fed  at  the  time  of  the  attack.  Of  the  four  children  under  six 
months  old,  three  had  never  been  nursed  and  one  was  breast  fed  for 
three  weeks  only. 

Of  the  5  infants  between  six  and  twelve  months  old,  one  received 
grocer's  milk,  one  condensed  milk  (a  change  to  Straus'  milk  having 
been  made  shortly  before  the  illness  began)  ;  one  was  fed  upon 
grocer's  milk  and  eggs ;  and  one  upon  bottled  milk,  macaroni,  eggs, 
bread  and  soup.  In  this  series  one  infant  had  been  nursed  to  within 
a  few  days  of  the  illness  and  the  change  of  nourishment  was  probably  a 


156  Louise  Cordes. 

predisposing  factor  in  determining  the  attack.  The  5  infants  from 
twelve  to  eighteen  months  old  received  "a  little  of  everything";  4  had 
been  breast-fed  to  ages  varying  from  twelve  to  sixteen  months;  2 
were  weaned  one  month  previous  to  the  beginning  of  illness;  1  was 
receiving  the  breast  in  addition  to  light  general  diet  at  the  time  of  the 
attack. 

The  10  children  ranging  from  eighteen  months  to  two  and  one-half 
years  had  all  been  breast-fed  for  from  nine  to  twenty  months. 

When  taken  ill  2  of  these  children  were  receiving  house  diet,  2  milk 
with  bread  or  cereals,  4  light  general  diet,  and  1  condensed  milk;  in 
one  case  the  food  was  not  recorded. 

In  the  2  cases  five  and  ten  years  old  no  special  cause  for  the  attack 
was  discoverable. 

As  to  environment,  under  which  term  are  included  cleanliness,  venti- 
lation, sunlight  and  care,  this  was  :  good  in  2  cases ;  fair  in  8 ;  poor  in 
7 ;  bad  in  3 ;  not  noted  in  6. 

The  duration  of  the  symptoms  before  the  cases  came  under  obser- 
vation was:  less  than  1  week  in  9;  1  week  in  4;  10  days  to  2  weeks 
in  4 ;  3  weeks  in  3 ;  1  month  to  five  weeks  in  3 ;  not  noted,  3. 

The  patients  were  under  observation :  less  than  1  week,  4 ;  1  week, 
3  ;  2  to  3  weeks,  8 ;  4  to  6  weeks,  3 ;  not  noted,  8. 

The  cases  are  grouped  under  three  heads  :  mild,  moderatelv  severe 
and  severe ;  of  the  latter  there  were  five  cases  all  of  which  terminated 
fatally.  This  classification  is  based  not  so  much  upon  the  frequency 
as  upon  the  character  of  the  stools  and  more  especially  upon  the  gen- 
eral constitutional  symptoms. 

The  mild  cases,  8  in  number,  were  those  the  number  of  whose  stools 
was  as  a  rule  four  to  seven,  consisting  of  green  and  yellow  feces  with, 
at  times,  a  slight  or  moderate  amount  of  mucus.  The  temperature, 
in  these  cases,  did  not  rise  about  ioo°,  tenesmus  was  absent  and  slight 
tympanites  rarely  present.  There  were  no  nervous  symptoms  and  re- 
covery occurred  in  from  one  week  to  two  months. 

In  the  13  cases  classed  as  moderately  severe,  the  stools  usually 
numbered  from  five  to  fifteen,  consisted  of  green  and  yellow  feces  with 
a  considerable  amount  of  mucus  and  in  two  cases  a  slight  admixture 
of  blood. 

The  temperature  as  a  rule  remained  below  1020  ;  tenesmus  and  nerv- 
ous symptoms  were  observed  at  times. 

In  the  5  severe  cases  the  stools  varied  from  seven  to  twelve,  at  times 
containing  blood  and  showing  in  three  cases  a  tendency  to  become 
watery.     The  temperature  ranged  from  subnormal  to  1060 ;  tenesmus 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  2  5 7 

and  tympanites  were  generally  marked  and  nervous  symptoms  promi- 
nent. 

The  treatment  was  chiefly  dietetic.  Calomel  and  castor  oil  were 
frequently  employed  and  bismuth  subnitrate  was  given  in  some  cases. 

Rectal  irrigation  of  saline  solution  was  employed  for  great  toxemia 
or  tenesmus. 

In  one  severe  case  the  serum  treatment  was  tried. 

A  brief  record  of  four  severe  and  fatal  cases  is  appended ;  the  fifth 
fatal  case  was  seen  in  the  Infirmary  Dispensary  and  died  one  day  later. 

M.  S.,  three  months  old;  condition  poor  at  the  beginning  of  the  attack. 
Brought  to  the  New  York  Infirmary  from  a  dirty,  practically  sunless,  poorly  ven- 
tilated tenement;  care  had  been  fair  and  there  had  been  no  previous  diarrhea. 
The  infant  had  been  nursed  three  weeks,  receiving  after  that  time  condensed 
milk  and  occasionally  zwieback. 

The  onset  was  by  vomiting.  On  admission:  anemic;  fontanel  depressed. 
Stools  seven  to  eight :  green  and  yellow  feces,  much  mucus,  no  blood.  Dis- 
charged at  the  end  of  two  weeks  cured. 

Readmitted  July  30th,  emaciated  and  much  prostrated  (attack  of  chicken 
pox  had  occurred  in  interim),  extremities  cold;  stools  six  to  ten,  brown  and 
watery,  no  mucus  and  no  blood;  temperature  range  from  subnormal  to  1030. 
One  day  after  admission  10  c.c.  of  the  "Harris"  anti-dysenteric  serum  were  in- 
jected and  this  was  repeated  on  two  succeeding  days.  A  diminution  in  the  num- 
ber of  stools  took  place  and  there  was  an  amelioration  of  the  general  symptoms 
which  in  all  probability  was  largely  due  to  energetic  stimulation.  On  the  third 
day  after  admission  the  physical  signs  of  broncho-pneumonia  were  noted  and 
death  followed  three  days  later. 

An  autopsy  revealed  acute  broncho-pneumonia  and  follicular  entero-colitis. 

L.  P.,  nine  months  old;  never  nursed;  he  received  besides  the  bottle,  mac- 
aroni, eggs,  bread  and  soup.  Condition  at  the  beginning  of  the  attack  fair,  but 
infant  rachitic.     No  previous  diarrhea ;    duration  of  the  attack  eleven  days. 

On  admission,  August  5th,  physical  signs  of  broncho-pneumonia. 

Fontanel  somewhat  depressed.  Ten  to  twelve  stools  in  twenty-four  hours : 
green,  feces,  very  little  mucus,  some  blood;  tympanites  present;  temperature 
101-1060;  nervous  symptoms  noted.  Under  observation  six  days.  Death  August 
nth.     Autopsy  showed  acute  broncho-pneumonia   and   follicular  colitis. 

The  Peyer's  patches  in  the  ileum  were  slightly  enlarged;  solitary  follicles  in 
the  colon  enlarged,  many  beginning  to  break  down  in  the  center.  Mesenteric 
lymph  nodes  moderately  enlarged. 

S.  D.,  four  months ;  never  breast-fed,  Straus'  milk  given  every  two  hours. 
Home  surroundings  and  care  fair.  No  previous  diarrhea.  Duration  of  illness 
one  week ;  onset  by  vomiting.  Admitted  to  Infirmary  on  September  7th. 
Anemic ;  rachitic ;  fontanel  slightly  depressed ;  tongue  coated ;  lungs  and  heart 
negative.  Four  to  ten  stools  consisting  of  semi-solid  green  and  yellow  feces, 
much  mucus  and  no  blood ;  tympanites  was  marked.  The  temperature  varied 
from  98-1040  F.  Death  occurred  on  September  28th.  An  autopsy  could  not  be 
obtained. 


158  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

S.  C,  four  months ;  never  nursed ;  fed  on  grocer's  milk.  Condition  at  the 
beginning  of  the  attack,  poor.  Surroundings  very  unfavorable  and  care  poor. 
No  previous  diarrhea.  Admitted  to  the  Infirmary  on  September  3d.  Duration 
of  illness  one  week.  Condition  on  admission :  anemic,  fontanel  depressed,  cir- 
culation poor.  Lungs  and  heart  negative;  five  to  ten  stools  a  day  consisting  of 
green  and  yellow  feces  with  much  mucus,  no  blood ;  no  tenesmus,  no  tympanites. 
Discharged  September  27th,  much  improved  and  steadily  gaining  in  weight. 
Brought  back  to  hospital  on  October  20th,  moribund;  death  occurred  on  the 
same  day.  The  second  attack  began  with  vomiting  three  days  before  admission. 
The  stools  were  green  and  watery  and  numbered  six  in  twenty-four  hours. 

Autopsy  showed  congestion  and  edema  of  the  lungs  and  ulcerative  colitis. 

In  conclusion,  I  desire  to  call  attention  to  the  frequent  occurrence  of 
the  Bacillus  dysenteric?  in  the  mildest  types  of  intestinal  disorder. 

It  is  interesting-  to  note  that  of  the  five  fatal  cases,  all  of  which  were 
under  nine  months  old,  not  one  had  been  breast-fed.  One  infant  was 
nursed  for  three  weeks  only. 

As  the  serum  treatment  was  employed  in  but  one  case,  no  opinion 
can  be  formed  as  to  its  efficacy. 

I  desire  to  thank  Dr.  Annie  S.  Daniel  and  Dr.  Ethel  Brown  for  plac- 
ing material  from  out-practice  cases  as  well  as  the  histories  of  the  same 
at  my  disposal.  Dr.  Marie  Grund  rendered  valuable  assistance  in  ob- 
taining complete  histories.  To  Dr.  R.  G.  Freeman's  courtesy  are  due 
the  records  obtained  from  the  Nursery  and  Child's  Hospital. 


CLINICAL    REPORT    OF    NINETEEN    CASES    OF    INTES- 
TINAL  INFECTION,   WITH   THE   BACIL- 
LUS  DYSENTERIC. 

BY   SAMUEL  AMBERG,    M.D.,    OF   BALTIMORE, 
Associate   in    Pediatrics,   Johns   Hopkins   University. 

The  total  number  of  cases  in  which  the  bacteriological  examination 
of  the  stools  was  made  was  47.  In  19  of  these  cases  the  Bacillus  dysen- 
terise  (Shiga)  was  found.  This  report  will  only  consider  positive 
cases. 

One  case  occurred  in  a  boy  nine  years  of  age.  All  of  the  other 
cases  were  under  two  years  of  age. 

Previous  attacks  of  diarrhea  were  noted  in  3  cases.  It  may  be  well 
to  call  attention  to  the  fact  that  satisfactory  histories,  in  regard  to 
this  point,  could  not  always  be  obtained. 

Food  at  the  Time  of  Attack. — In  only  one  instance  did  the  food 
consist  of  breast  milk  alone.  Several  other  infants  had  breast  milk,  but 
also  in  addition  other  food,  often  improper.  The  hygienic  surroundings 
and  the  care  given  to  the  patients  were,  in  many  instances,  poor.  The 
food  was  evidently  improper  in  6  cases ;  in  5  the  food  had  been  regu- 
lated by  the  family  physician.  One  patient  who  had  suffered  from  diar- 
rhea during  the  previous  summer  was  on  a  very  strict  regimen. 

In  regard  to  the  quality  of  the  cow's  milk  given,  it  may  be  stated 
that  those  seen  in  private  practice  received  bottled  milk  from  the 
best  dairies  in  town.  Of  the  other  cases  one  received  grocery  milk, 
while  the  supply  of  the  remainder  was  not  ascertained. 

Exciting  Cause  of  the  Attack. — The  chief  factors  entering  into 
consideration  are  the  feeding  and  the  hygienic  conditions.  In  6  cases 
taken  from  private  practice  there  is  no  apparent  reason  to  assume  such 
a  cause.  In  the  dispensary  cases,  which  represent  the  poorer  classes, 
both  the  feeding  and  the  conditions  of  life  were  such  that  it  was  not 
surprising  to  see  these  infants  the  subjects  of  gastro-intestinal  disturb- 
ance. 

Type  of  Disease. — The  classification  of  5  cases  of  the  total  18  (the 
case  of  the  boy  of  nine  years  being  omitted)  as  mild,  rests  on  the  facts 


160  Samuel  Amber g. 

that  the  condition  of  the  infants  at  the  time  of  observation  was  good  or 
fairly  good ;  that  the  number  of  passages  had  not  exceeded  twelve  in 
twenty-four  hours,  and  that  with  the  exception  of  i  case  tenesmus 
was  absent.     Furthermore,  blood  was  not  present  in  the  passages. 

The  course  of  the  disease  could  not  be  followed  in  2  cases  ;  2  others 
recovered  in  three  to  four  weeks.  In  only  one  case  was  vomiting 
a  marked  symptom.  In  this  the  recovery  was  not  complete  after 
fifty-one  days'  observation,  though  the  symptoms  were  never  severe. 
The  number  of  leucocytes  in  the  dejecta  varied  much,  but  sometimes 
they  were  very  numerous. 

The  condition  of  the  7  cases  classified  as  moderately  severe  was 
good  in  5,  fairly  good  in  1,  and  poor  in  1  case.  The  number  of  pas- 
sages varied  from  ten  to  twenty  in  twenty-four  hours ;  tenesmus  was 
present  in  3  cases,  absent  in  4.  Xone  of  the  babies  vomited  very  much. 
The  passages  usually  contained  small  amounts  of  fecal  matter  and 
curds.  The  amount  of  mucus  was  considerable.  The  number  of  leuco- 
cytes was  great,  and  with  the  exception  of  two  cases  more  or  less 
pus  was  discernible  to  the  eye,  but  rarely  after  the  third  day  of  obser- 
vation, and  then  only  in  small  quantity. 

Blood  was  noted  in  the  passages  of  all  cases  but  one.  This  case 
was  placed  in  this  group  mainly  on  account  of  the  course  of  the  dis- 
ease, during  which  the  weight  dropped  from  12  lbs.  1  ounce  to  8  lbs. 
9  ounces. 

There  were  6  classified  as  severe.  The  condition  of  these  was  good 
in  2,  fairly  good  in  2  and  poor  in  2.  The  stools  of  these  patients  were 
usually  frequent,  four  to  sixteen  in  twenty-four  hours.  Here,  too,  vom- 
iting was  not  a  prominent  feature.  Tenesmus  was  present  in  all  cases 
but  one,  and  one  child  seemed  to  have  constant  pain  in  the  abdomen. 
In  general  the  character  of  the  passages  did  not  differ  materially  from 
those  of  the  moderate  group.  One  case  did  not  have  blood  in  the 
stools,  but  the  severe  course  of  the  disease  places  it  in  this  group.  One 
was  classified  as  a  severe  case  on  account  of  the  amount  of  pus  pres- 
ent in  the  stools  and  the  protracted  course  of  the  disease  accompanied 
by  considerable  emaciation.  The  amount  of  blood  in  the  stools  of  these 
patients  was  never  large  and  never  were  there  any  clots.  Pus  was  con- 
stantly present  in  one  case,  though  in  varying  amount,  and  the  number 
of  the  passages  did  not  decrease  materially  during  the  course  of  the 
disease. 

Type  of  Organism, — The  type  of  dysentery  bacillus  found  in  17  of  the 
18  cases  was  the  "Flexner-Harris"  or  acid-producing  type  and  in  1  the 
true  Shiga  type  was  isolated. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  161 

Of  the  1 8  positive  cases,  4  died.  The  disease  in  one  took  a  rapid 
course  and  was  associated  with  a  high  temperature.  The  autopsy  of 
one  case  revealed  the  typical  lesions  of  a  follicular  ileo-colitis. 

Serum  Treatment. — There  were  in  all  10  cases  treated  by  the  injec- 
tion of  serum.  This  does  not  include  the  boy  nine  years  old,  who  died 
despite  several  injections  of  "Shiga"  serum. 

All  patients  with  one  exception  were  injected  on  the  first  day  of  ob- 
servation.    The  exception  was  Case  IX,  injected  on  the  third  day. 

A  short  description  of  each  case  follows  : 

I. — Poorly  nourished  infant,  seven  months  old.  Moderately  ill  two  weeks 
before  coming  under  observation.  Given  "Harris"  serum,  10  c.c,  on  four  occa- 
sions. In  twelve  days  discharged  apparently  cured.  "Flexner-Harris"  organism 
isolated. 

II. — Poorly  nourished  infant,  five  months  old.  Sick  one  week  before  coming 
to  dispensary.  Under  treatment  one  month,  during  which  time  "Shiga"  serum 
was  given  four  times,  50  c.c.  in  all.  Infection  was  with  the  "Flexner-Harris"  type 
of   organism.      Fatal   termination. 

III. — Well  nourished  chdd,  twelve  months  old;  observed  on  the  first  day  of 
attack.  Severely  infected  with  the  true  Shiga  type  of  organism.  "Harris"  serum 
given,  10  c.c,  two  different  times.     Child  made  a  good  recovery  in  ten  days. 

IV. — Well  nourished  child,  nineteen  months  old ;  seen  on  second  day  of  at- 
tack; given  "Harris"  serum,  10  c.c,  three  times.  Was  moderately  ill  and  under 
observation  one  month,  at  the  end  of  which  time  he  was  discharged  cured. 
"Flexner-Harris"    organism   obtained   from   stools. 

V. — Fairly  nourished  child,  six  months  old,  who  had  been  moderately  ill  for 
one  month  before  treatment;  had  two  injections  of  serum.  He  received  10  c.c. 
of  "Harris"  serum  on  one  occasion  and  10  c.c.  of  "Seward"  serum  on  another. 
The  infection  was  of  the  "Flexner-Harris"  type.  He  was  under  treatment  six 
weeks  and  was  discharged  improved  but  not  entirely  well. 

VI. — Well  nourished  child  of  nineteen  months.  Seen  on  the  fourth  day  of  a 
moderately  severe  attack.  "Flexner-Harris"  type  of  organism  isolated.  Treated 
by  injection  of  "Seward"  serum,  15  c.c,  on  two  occasions.  Discharged  cured 
in  eight  days. 

VII. — Fairly  nourished  child,  eighteen  months  old.  Had  been  severely  sick 
four  days  with  a  "Flexner-Harris"  infection.  Received  10  c.c.  of  "Shiga"  serum 
on  the  first  and  second  days  of  observation.  No  benefit  seen  from  this.  Was 
discharged  at  the  end  of  a  month  and  a  half,  improved. 

VIII. — Twenty  months  old.  Well  nourished;  sick  six  days  before  coming 
under  observation  and  under  observation  twenty  days.  Ten  c.c.  of  "Seward" 
serum  given  on  the  first  and  second  clays  of  observation.  Discharged  cured  in 
twenty   days.     "Flexner-Harris"  type  of   infection. 

IX. — Twenty  months  old ;  well  nourished.  Sick  one  week  before  coming 
under  observation.  Was  given  "Shiga"  serum,  20  c.c.  and  "Seward"  serum,  25 
c.c,  in  five  successive  injections.  No  improvement  and  the  child  died  at  the  end 
of  seventeen  days.     "Flexner-Harris"  type  of  infection. 

X. — Ten  months  old ;  well  nourished ;  sick  ten  days  before  coming  under  ob- 
servation,  but    only    moderately    so.     Was     given   two   injections   of  25   c.c   of 


1 62  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

"Seward"  serum.     Child  discharged  cured  in  five  days.     "Flexner-Harris"  type 
of  organism  isolated. 

The  small  number  of  cases  under  observation  and  the  fact  that  the 
usual  treatment  was  given  beside  the  serum  makes  it  impossible  to  draw 
definite  conclusions  in  regard  to  the  effect  of  serum  treatment.  Case 
III.  improved  very  rapidly  after  the  administration  of  serum,  but  in 
none  of  the  others  was  any  striking  benefit  noticed.  No  ill  effects  were 
seen  in  anv  case. 


REPORT  OF  SEVEN  CASES  OF  INTESTINAL  INFECTION 
WITH  THE  BACILLUS  DYSENTERIAE   (SHIGA)   OC- 
CURRING  AT    THE    NEW    YORK    FOUNDLING 
HOSPITAL,  WHICH  WERE  TREATED  WITH 
ANTIDYSENTERIC  SERUM. 

BY   ROWLAND   G.    FREEMAN,    M.D., 
Attending  Physician  to  the  New  York  Foundling  Hospital. 

Case  I. — Seven  months  old,  admitted  June  15,  1903.  A  poorly  nourished, 
rachitic  child,  weighing  only  9  lbs.  He  had  diarrhea ;  the  stools  were  green, 
with  mucus  and  curds,  occasionally  fluid,  three  to  five  in  twenty-four  hours. 
There  was  no  vomiting,  temperature  between  97.50  F.  and  100.50  F.  This  con- 
dition persisted  for  one  month. 

On  July  17th  his  temperature  began  to  rise,  fluctuating  between  ioo°  F.  and 
1050  F.  The  stools  did  not  increase  in  number,  but  on  July  21st  began  to 
contain  blood,  which  soon  became  very  abundant.  The  B.  dysenteries  was  iso- 
lated from  the  stools.  He  was  given  "Harris"  serum,  10  c.c,  on  six  successive 
days.  Blood  continued  for  seven  days  and  then  disappeared.  The  stools  were 
from  two  to  five  a  day,  and  after  two  weeks  improved  very  much  in  character, 
so  that  they  were  yellow,  brown  and  formed,  though  still  containing  some 
mucus.  Thereafter  there  was  no  rise  in  temperature.  His  weight  varied  but 
slightly  for  the  next  three  months,  a  few  ounces  being  gained  and  then  lost. 
He  eventually  died  of  marasmus  on  November  6th.  No  autopsy  was  obtained. 
In  this  case  there  seemed  to  be  some  benefit  from  the  use  of  the  serum,  but 
the  child  was  unable  to  overcome  his  marantic  condition. 

Case  II. — A  well-nourished  child,  seven  months  old,  suddenly  became  ill 
with  temperature  of  1030  F.,  rising  in  twenty-four  hours  to  104.80  F.  The 
stools  at  first  were  brown  and  loose,  two  to  four  a  day.  The  temperature  then 
dropped  to  normal,  and  after  three  days  the  stools  were  normal  for  twenty- 
four  hours ;  but  a  day  later  a  relapse  occurred,  the  stools  became  frequent  and 
green,  with  mucus  and  blood,  and  the  temperature  rose  to  1030  F.  The  child 
thereafter  lost  ground  rapidly  and  died,  despite  the  injection  of  10  c.c.  of 
"Harris"  and  10  c.c.  of  "Seward"  serum.  The  temperature  for  the  last  three 
days  was  considerably  elevated. 

The  B.  dysenteries  was  found  in  the  stools  five  days  before  death,  and  was 
also  cultivated  from  the  post-mortem  scrapings  of  the  intestinal  mucosa.  The 
autopsy  showed  an  acute  ileo-colitis  with  superficial  necrosis  and  hemorrhages. 

Case  III. — One  year  old.  Following  measles  and  after  her  temperature  had 
become  normal  there  occurred  numerous  green  mucous  stools,  without  blood ; 
from  these  the  B.   dysenteries  was  isolated.     The  temperature  at  first  was  very 


1 64  Rowland  G.  Freeman. 

high,  varying  between  ioo°  F.  and  104.6°  F. ;  after  seven  days  it  fell  to  normal. 
Blood  was  present  in  the  stools,  but  never  in  considerable  quantity.  There 
were  never  more  than  five  stools  in  twenty-four  hours.  She  was  given  on 
successive  days  "Seward,"  "Harris,"  and  '"Shiga"  serum,  100  c.c.  in  all.  There 
was  no  improvement  seen  from  the  injections  and  her  temperature  during  the 
last  ten  days  was  very  irregular,  occasionally  reaching  104°  F.  The  disease 
was  complicated  by  the  development  of  diphtheria  one  week  before  death.  As 
{his  was  laryngeal,  pneumonia  had  developed  before  it  was  discovered  and 
diphtheria  antitoxin  was  used  too  late  to  be  effective.  Death  occurred  twenty 
days  after  the  beginning  of  diarrhea. 

The  autopsy  showed  membranous  ileo-colitis. 

Case  IV — A  very  small,  poorly  nourished  child,  fifteen  months  old,  weigh- 
ing 12  lbs.,  was  suddenly  taken  ill  with  green,  mucous  stools.  There  was  no  vom- 
iting;  temperature  below  100'  F.  until  the  twelfth  day,  when  blood  appeared 
in  the  stools,  and  coincident  with  this,  a  rise  in  temperature  to  103°  F.  Culture 
showed  B.  dysenteric.  He  was  given  Shiga  serum,  10  c.c,  on  five  successive 
days,  but  the  temperature  did  not  fall,  remaining  about  ioi°  F.  and  the  frequent 
mucous  green  stools  with  blood  continued.  He  died  one  week  later.  Xo 
autopsy. 

Case  V. — A  very  poorly  nourished  child,  seventeen  months  old.  weighing 
13^2  lbs.,  was  brought  to  the  hospital  with  the  following  history:  He  had  been 
sick  for  several  weeks  with  loose  brown  stools  containing  mucus  but  no  blood. 
He  had  been  losing  weight  and  had  been  feverish  for  some  time.  His  tem- 
perature after  admission  was  irregular,  but  for  the  first  four  weeks  that  he 
was  under  observation,  never  high.  An  examination  of  the  stools  failed  to 
show  the  presence  of  the  B.  dysenteries.  At  the  end  of  three  weeks  his  tem- 
perature began  to  rise,  the  stools  to  become  more  frequent  and  to  contain  an 
increased  quantity  of  mucus  and  a  small  amount  of  blood.  He  was  given 
on  successive  days  ''Harris"  or  "Shiga"  serum  until  he  had  had  in  all  75  c.c.  of 
"Harris"  and  30  c.c  of  "Shiga"  serum ;  the  blood  disappeared  from  the  stools 
and  the  temperature  fell  almost  to  normal,  but  he  died  with  general  edema  and 
marked  emaciation.  B.  dyscnterice  was  found  in  the  stools  five  days  before 
death.     Xo  autopsy. 

Case  VI. — A  fairly  nourished  child  nine  months  old  was  brought  to  the 
hospital,  having  had  an  attack  of  measles  one  week  before.  She  had  a  high 
temperature  (1040  F.)  and  frequent  green  watery  stools,  containing  at  times 
mucus  and  a  slight  amount  of  blood.  There  was  only  a  little  vomiting.  Examina- 
tion of  the  stools  for  B.  dysenteries  gave  a  positive  result.  "Seward"  serum  was 
given.  5  or  10  c.c,  on  successive  days,  without  affecting  in  the  slightest  way  the 
course  of  the  disease.  Her  temperature  remained  constantly  high,  between  ioi°  F. 
and  103'  F.  The  frequent  stools  continued,  prostration  became  very  marked 
and  she  developed  signs  of  broncho-pneumonia  and  died  after  fifteen  days  of 
observation.     In  all  106  c.c  of  serum  were  given.     Xo  autopsy. 

Case  VII. — A  nursing  child,  one  year  old,  was  taken  suddenly  ill  with  fre- 
quent greenish-yellow  stools,  four  to  six  a  day.  They  contained  blood  and  mucus. 
There  was  no  vomiting.  Temperature  not  high,  averaging  Cj8°-iooI/4°  F. 
B.  dysenteries  was  found  in  the  stools.  She  was  given  "Shiga"  serum,  35  c.c.  in 
all,  in  5  c.c.  doses.     At  the  end  of  sixteen  days  there  was  a  sudden  rise  of  tern- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  165 

perature  to  1040  F.,  and  it  remained  high  for  four  days,  but  after  this  fell 
to  normal.  The  stools  gradually  became  normal  in  appearance  and  the  case 
went  on  to  complete  recovery. 

From  an  examination  of  the  reports  it  does  not  appear  that  there 
was  demonstrated  in  any  a  marked  curative  effect  from  the  serum. 
Case  I.  was  undoubtedly  improved  by  it  and  Case  V.  to  a  less  degree; 
but  both  of  these  eventually  died  of  marasmus  some  time  after  the  sub- 
sidence of  their  intestinal  symptoms.  Case  III.  was  complicated  by 
diphtheria  and  broncho-pneumonia  and  death  was  due  directly  to  these 
complications.  Cases  II.,  IV.,  and  VI.  died  as  a  direct  result  of  the 
intestinal  disease ;  one  of  these  chilllren,  however,  was  in  wretched  con- 
dition before  the  attack  and  incapable  of  withstanding  any  serious  ill- 
ness. Almost  all  of  the  children  were  poorly  nourished  infants  of  the 
type  known  as  "institution  children"  and  their  failure  to  respond  satis- 
factorily to  any  remedial  measures  is  not  surprising.  The  only  re- 
covery was  in  a  well-nourished,  breast-fed  infant,  with  a  mild  type  of 
infection. 


SEVEN   CASES   OF  INTESTINAL  INFECTION  '  WITH   THE 

BACILLUS  DYSENTERIAE  TREATED  BY  SERUM 

INJECTIONS. 

BY  LOUIS   M.   WARFIELD,   M.D., 
Savannajj,  Ga. 

The  cases  here  reported  were  observed  and  treated  by  the  writer  in 
New  York  City  during  July  and  the  first  half  of  August,  1903.  The 
object  of  the  investigation  was  to  study  the  cases  of  Shiga  infection 
of  the  intestine  in  infants.  It  was  the  writer's  duty  to  see  cases  in  the 
tenements  especially  on  the  East  Side  and  to  use  the  serum  as  much  as 
possible  in  those  cases  that  were  proven  by  bacteriological  examina- 
tion to  be  cases  of  .Shiga  infection.  It  was  hoped  that  a  large  number 
of  acute  cases  could  be  observed  and  followed  by  visiting  the  patients 
in  their  own  homes.  It  was  soon  seen,  however,  that  it  was  impossible 
to  treat  any  considerable  number  of  cases  principally  for  the  reason  that 
there  was  comparatively  little  illness  among  the  babies  in  the  tenements. 
The  cases  that  occurred  were  mostly  of  a  mild  type  so  that  the  with- 
drawal of  the  breast  or  cow's  milk  and  a  purge  soon  accomplished  a  cure. 
The  very  mild  cases  and  a  number  almost  moribund  when  first  seen 
were  not  considered  suitable  for  observation  and  so  were  not  treated  by 
serum  injection.  The  cases  were  not  taken  in  order  but  the  severe  ones 
alone  were  tabulated  and  as  far  as  possible  carefully  followed.  In  all 
cases  where  the  serum  was  used  specimens  of  stools  were  examined  by 
Drs.  Gay  and  Stanton  (see  report).  Much  difficulty  was  experienced 
in  getting  fresh  specimens  for  them  as  the  cases  were  at  times  several 
miles  from  the  laboratory.  The  various  avenues  for  contamination 
of  specimens  and  the  long  time  frequently  elapsing  between  the  pass- 
ing of  the  stool  and  the  plating  of  it  in  the  laboratory  will  account  for 
the  fact  that  many  cases  that  appeared  clinically  to  be  typical  infec- 
tions with  the  bacillus  of  dysentery  failed  to  show  the  specific  organism 
and  so  were  not  available  for  record  though  treated  with  the  serum. 

Again  it  must  be  borne  in  mind  that  the  difficulties  of  injecting  the 
serum  in  suitable  cases  in  the  tenements  were  great ;  the  apparent  pam 
caused  and  the  visible  swelling  produced  by  the  injection  of  10  or  20  c.c. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  167 

of  fluid  beneath  the  skin  were  in  many  cases  too  much  for  the  mother's 
feelings  and  so  one  injection  was  often  all  that  could  be  made. 

The  cases  were  treated  in  the  usual  manner,  that  is  to  say,  nursing  at 
the  breast  or  cow's  milk  was  discontinued  and  barley  water  substituted 
until  the  acute  symptoms  had  subsided.  Some  purgative — castor  oil 
or  calomel  was  given.  Occasionally  bismuth  or  a  chalk  mixture  was 
later  administered.  Other  drugs  were  rarely  used.  A  short  history  of 
each  case  follows : 

Case  I. — J.  K.,  three  and  one-half  months  old;  tenement-house  patient.  A 
Mongolian  idiot,  poorly  nourished,  had  been  bottle  fed  with  grocery  milk  since 
birth.  Duration  of  illness,  four  days;  onset  with  vomiting  and  fever;  twelve  to 
fifteen  loose,  bloody,  mucous  stools  a  day;  some  tenesmus.  There  was  marked 
anemia ;  sunken  fontanel ;  cold  extremities ;  some  patches  of  broncho-pneumonia 
over  both  lungs  behind.  Temperature,  I02°-I04°  F. ;  pulse,  140-160.  He  was 
given  8  c.c  of  "Harris"  serum.  No  noticeable  change  in  the  number  or  char- 
acter of  the  stools  during  the  succeeding  twenty-four  hours.  On  the  next 
day  5  c.c.  of  "Harris"  serum  was  given.  During  the  next  twenty-four  hours 
there  were  only  three  stools  of  the  same  character.  The  child's  general  condi- 
tion was  worse.  Was  again  given  5  c.c.  of  the  same  serum.  Death  in  twenty- 
four  hours.  The  serum  was  given  in  this  case  to  see  if  it  could  affect  the 
existing  intestinal  infection  and  so  possibly  aid  the  child  to  recover  from  the 
broncho-pneumonia,  which  was  the  chief  disease.  The  Bacillus  dysenteries 
("Flexner-Harris"  type)  was  found  in  the  stools. 

Case  II. — L.  B.,  eight  months  old ;  tenement-house  patient.  Child  breast 
fed  and  in  addition  was  given  grocery  milk.  Duration  of  the  illness  before 
observation,  two  days.  Onset  with  vomiting,  fifteen  to  twenty  fluid  stools,  with 
mucus,  no  blood.  General  condition  fair;  surroundings  filthy.  Temperature, 
101.8°  F.  Pulse,  128.  He  was  given  10  c.c.  of  "Harris"  serum.  The  next  day 
there  were  eight  stools,  the  character  the  same;  temperature,  ioo°  F.  General 
condition  unchanged.  On  the  following  day  the  temperature  was  101.80  F. ; 
pulse,  180.  Five  stools  in  the  twenty-four  hours,  several  of  which  contained 
blood.  Was  given  6  c.c.  of  "Harris"  serum,  after  much  persuasion.  During 
the  next  twenty-four  hours  there  were  three  stools,  color  watery  green,  much 
fecal  matter  and  curds,  some  mucus,  no  blood.  Mother  was  found  on  two 
successive  visits  nursing  the  child  against  advice.  She  took  child  to  a  doctor, 
who  gave  her  some  medicine  and  told  her  to  feed  the  baby  milk.  The  case 
was  dismissed,  as  the  mother  refused  to  follow  advice.  The  child  undoubt- 
edly improved  under  the  serum,  but  it  is  impossible  to  say  that  all  the  im- 
provement was  due  to  the  serum.  The  Bacillus  dysenteries  ("Flexner-Harris") 
was  found  in  the  stools. 

Case  III. — G.  B.,  ten  months  old;  Bellevue  Hospital.  Child  was  a  foundling 
and  no  history  could  be  obtained.  When  first  seen  the  child  was  almost  mori- 
bund ;  there  was  a  film  over  the  eyes ;  marked  emaciation ;  retracted  abdomen ; 
the  temperature  was  100.20  F.  Pulse  not  perceptible ;  breathing  was  labored. 
Was  given  digitalis  and  brandy,  and  20  c.c.  of  "Harris"  serum  on  July  22d, 
at  1 :3c  P.M.  At  7  130  P.M.  the  condition  seemed  a  trifle  better,  one  stool  fluid, 
brownish,  foul,  no  mucus  or  blood;  temperature,  however,  had  risen  to  104.80  F. 


1 68  Louis  M.  JVaiHeld. 

Twenty  c.c.  of  ''Harris"  serum  again  injected.  During  the  night  the  condition 
improved  somewhat.  Was  sponged  with  alcohol,  after  which  the  child  slept 
for  nine  hours,  only  being  aroused  to  take  albumen  water,  which  he  did  well. 
The  pulse  became  perceptible  now  and  then,  and  it  was  possible  to  count  it. 
Voided  some  urine.  Two  dark  greenish  and  brownish  stools  were  passed, 
containing  mucus  and  blood.  On  July  23d  the  condition  was  distinctly  im- 
proved. Temperature,  98.6°  F.  Pulse  better,  but  still  hard  to  count;  extremities 
cold,  but  the  circulation  was  slightly  improved  and  child  more  quiet.  At  II  A.M., 
20  c.c.  of  "Harris"  serum  was  given.  At  6  P.M.,  conditions  not  so  good.  Tem- 
perature, 1010  F.  Pulse  not  good;  breathing  labored.  No  vomiting;  three 
brown,  watery  stools  in  the  last  six  hours;  no  mucus  and  no  blood.  At  7:45 
P.M.,  20  c.c.  more  of  "Harris"  serum  given.  Following  morning  was  mori- 
bund, pulse  imperceptible,  profound  toxemia ;  death  at  5  A.M.  Bacillus  dys- 
enteric ("Flexner-Harris"  type)  was  isolated  from  the  stools.  In  this  case 
the  injection  of  serum  seemed  to  be  followed  by  a  decided  but  temporary  im- 
provement. 

Case  IV. — R.  S.,  six  months  old;  Bellevue  Hospital.  Duration  of  illness 
two  days,  and  the  onset  was  with  vomiting  and  loose  mucous  and  bloody  stools, 
ten  to  fifteen  in  twenty-four  hours,  with  some  tenesmus.  The  general  condi- 
tion was  good.  He  was  given  10  c.c.  of  "Shiga"  serum  on  admission,  July  28th, 
at  5  -.30  P.M.  The  temperature  at  9  P.M.  was  1020  F.  Castor  oil  given.  July 
31st,  August  1st,  4th  and  5th  he  had  10  c.c.  of  "Shiga"  serum.  On  August  6th, 
nth,  12th,  and  13th,  he  had  20  c.c.  of  "Shiga"  serum.     He  did  not  improve. 

At  times  he  was  bright,  but  relapsed  into  a  whining,  restless  condition.  The 
stools  after  the  first  injection  were  never  more  than  six  in  twenty-four  hours, 
but  they  occasionally  were  streaked  with  blood.  His  condition  grew  worse  in 
spite  of  large  and  repeated  doses  of  serum.  He  died  a  few  days  later.  Bacillus 
dysenteries  (true  Shiga  type)  was  found  in  the  stools.  At  autopsy  numerous 
follicular  ulcers  were  found  in  the  descending  colon  and  sigmoid  flexure  and 
the  mesenteric  glands  were  swollen.  There  were  also  patches  of  broncho- 
pneumonia in  the  lungs. 

Case  V. — M.  D.,  ten  months ;  Bellevue  Hospital.  No  previous  history  could 
be  obtained.     Condition  when  seen  on  July  30th  was  good. 

Stools  were  four  a  day,  small,  semi-solid,  with  mucus,  no  blood.  Tempera- 
ture 990  F.  Was  given  10  c.c.  of  "Harris"  serum.  For  the  next  three  days 
the  stools  were  five  to  six  a  day,  and  some  contained  pus,  no  blood  at  any 
time.  The  condition  remained  good.  She  was  given  20  c.c.  of  "Harris"  serum 
on  August  5th  and  again  on  the  6th.  Stools  were  then  four  to  five  a  day, 
no  curds,  no  mucus,  no  pus,  no  blood.  Child  was  doing  very  well  and  later 
was  discharged  cured. 

B.   dysenteries    ("Flexner-Harris"   type)    was   found   in   the   stools. 

Case  VI. — B.  F.,  eight  months  old;  Bellevue  Hospital;  no  history  could 
be  obtained.  Was  seen  on  July  30th.  Stools  were  from  three  to  eight  in  twenty- 
four  hours,  loose,  contained  mucus  and  at  times  blood.  Temperature  never 
exceeded  ioo°  F.  She  had  castor  oil  and  colon  irrigations  and  later  bismuth. 
She  did  not  do  as  well  as  expected  and  on  August  4th  she  was  given  15  c.c. 
of  "Harris"  serum.  Again  on  the  15th  she  was  given  20  c.c.  of  "Harris"  serum 
and  on  the  17th  20  c.c.  of  "Shiga"  serum.  The  stools  after  the  last  injection 
became   better;    they   were   four   to   six   a   day,   containing   some   mucus   but   no 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  169 

blood.  The  general  condition  improved  very  much  and  she  was  discharged 
on  August   14th  cured. 

Bacillus  dysenterice   ("Flexner-Harris"  type)   was  recovered  from  the  stools. 

Case  VII. — A.  C,  two  months  old;  Bellevue  Hospital;  no  history  could 
be  obtained.  The  patient  was  extremely  ill  when  admitted  on  August  6th. 
Some  prostration  and  the  extremities  were  cold.  She  was  given  castor  oil  and 
brandy.  Stools  were  three  to  four  a  day,  of  foul  odor,  with  mucus,  no  blood.  On 
August  10th  the  child's  condition  was  worse.  The  stools  contained  consider- 
able blood.  She  was  given  20  c.c.  of  "Shiga"  serum  at  2  P.M.  and  again  at 
6  P.M.,  but  the  patient  did  not  rally.  Coma  set  in  and  death  shortly  super- 
vened. The  temperature  was  subnormal.  Dysentery  bacilli  of  the  '"Flexner- 
Harris"   type   were   found   in   the   stools. 

It  will  be  seen  that  of  these  7  cases  4  were  fatal  and  3  were  cured 
or  very  much  improved.  Of  the  fatal  cases  2  were  practically  mori- 
bund when  first  seen  and  the  serum  was  given  without  the  expectation 
of  improving  matters  very  much. 

Case  IV,  although  seen  early  in  the  attack  and  given  serum  at  once, 
after  apparently  improving  suffered  a  relapse  and  after  daily  serum 
injections  amounting  in  all  to  150  c.c,  gradually  sank  and  died.  This 
was  a  case  in  which  one  might  have  expected  a  response  to  the  serum. 

The  impression  gained  from  the  use  of  the  serum  was  that  in  chil- 
dren, at  least  in  these  cases,  it  did  not  have  a  curative  value.  No  ill 
effects  of  any  kind  were  noted  after  the  injections.  As  far  as  could 
be  seen  there  was  no  rise  or  fall  of  temperature  directly  due  to  the 
serum  or  change  in  pulse  rate  except  in  the  pulseless  cases  where  brandy 
and  other  stimulants  were  also  given.  The  injections  also  seemed 
to  cause  great  pain  which  may  have  been  due  to  the  preservative  but 
also  to  the  distension  of  the  tissues.  The  pain  soon  disappeared  and 
the  serum  was  in  most  cases  rapidly  absorbed  leaving  only  a  slight  sore- 
ness on  pressure  for  about  24  hours  at  the  place  of  injection.  No  erup- 
tions were  noted  in  these  cases  and  no  infections  were  seen.  The  back 
was  usually  the  spot  selected  for  these  injections.  The  amount  varied 
from  10  c.c.  to  150  c.c.  Some  cases  were  given  20  c.c.  at  a  time  but 
10  c.c.  was  the  amount  usually  used. 


REPORT  OF  TWENTY-EIGHT  CASES  OF  INFECTION  WITH 

THE  BACILLUS  DYSENTERIAE  IN  INFANTS 

AND  YOUNG  CHILDREN. 

BY  ROBERT  \Y.   HASTINGS,  M.D., 
Physician  to  the  Boston  Floating  Hospital. 

During  the  summer  of  1903  there  were  observed  twenty-eight  cases 
of  infection  with  the  Bacillus  dysenteriae  in  young  children  in  the  Bos- 
ton Floating  Hospital.  Thirty-five  cases  in  all  were  examined  bac- 
teriologically. 

The  Boston  Floating  Hospital  received  cases  from  dispensaries  and 
hospitals  and  also  those  referred  by  private  physicians.  It  is  a  boat 
fitted  up  with  wards  for  permanent  and  transient  cases  and  thus  it  was 
possible  to  keep  patients  under  constant  observation.  In  the  permanent 
wards  almost  all  the  cases  were  severe  ones.  The  cases  making  up  this 
report  were  all  observed  in  the  permanent  wards  and  hence  the  pre- 
ponderance of  what  will  be  later  described  as  the  severe  cases. 

At  first  those  stools  containing  blood  and  mucus  were  examined  bac- 
teriologically,  later  on  account  of  stress  of  work  only  those  from  the 
severest  cases.     There  was  no  examination  of  consecutive  cases. 

The  bacteriological  work  was  in  charge  of  Air.  Arthur  I.  Kendall 
(see  report).  The  patients  were  all  from  the  tenement  house  class 
though  many  were  not  from  the  very  poorest. 

Thirty-five  cases  we^e  carefully  studied  and  in  twenty-eight  the  pres- 
ence of  the  Bacillus  dysenteriae  was  demonstrated. 

Negative  Cases. 

In  three  of  the  seven  negative  cases  no  cause  could  be  assigned  for 
the  failure  to  find  the  bacillus  dysenteriae.  Two  were  evidently  cases 
of  meningitis  probably  tuberculous.  One  was  a  case  of  general  miliary 
tuberculosis  the  tubercle  bacilli  being  demonstrated  in  the  stools.  One 
was  a  case  of  typhoid  fever  and  from  the  stools  of  the  patient  two 
years  old  the  typhoid  bacillus  was  cultivated. 

Positive  Cases. 
Previous  Attacks  of  Diarrhea. — The  histories  obtained  were  in  many 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  171 

instances  unreliable.  In  four  cases  only  was  there  a  history  of  previous 
enteric  disturbance.  Of  these  cases  three  gave  histories  of  previous 
attacks  of  diarrhea  during  the  earlier  summer.  One  case  had  had  two 
previous  attacks,  one  in  the  summer  of  1902  and  a  second  earlier  in 
the  season  of  1903. 

Character  of  the  Food  at  Time  of  Attack. — Two  were  breast-fed  ex- 
clusively ;  live  cases  were  fed  on  condensed  milk  alone ;  three  received 
ordinary  table  diet;  cow's  milk  diluted  with  water  or  thin  gruels  with- 
out regard  to  accurate  modification  had  been  given  to  seven ;  proprietary 
foods  alone  had  been  given  to  three,  in  combination  with  milk  to  four ; 
a  restricted  diet  of  bread,  beef  juice  and  milk  had  been  given  to  three. 
In  one  case  the  diet  was  not  stated. 

Apparent  Cause  of  Attack. — No  one  cause  can  be  assigned  to  any 
case  with  a  single  exception.  In  most  of  the  cases  the  food  of  the 
children  lacked  even  ordinary  care  in  its  method  of  preparation.  The 
milk  was  the  usual  milk  of  the  household,  in  many  instances  kept  in 
unhygienic  surroundings.  In  no  case  had  the  food  been  sterilized  be- 
fore being  given  to  the  child.  In  one  case,  a  breast-fed  child,  the  onset 
seemed  to  be  synchronous  with  the  use  of  the  breast  pump. 

Ages  and  Duration  of  Attack. — The  average  duration  of  symptoms 
before  coming  under  observation  was  seven  days.  The  longest  period 
was  six  weeks. 

The  average  period  of  observation  was  eighteen  days.  The  shortest 
was  in  three  patients  who  died  on  the  day  of  entrance.  The  longest 
period  of  observation  was  sixty-three  days.  The  average  age  was  ten 
months,  the  youngest  being  three  months  and  the  oldest  four  years. 

Character  of  Attacks. — Of  the  positive  cases  three  are  noted  as  mild, 
five  as  of  moderate  severity  and  twenty  as  severe.  Those  cases  were 
considered  mild  whose  temperature  was  100. 5 °  F.  or  lower,  whose 
constitutional  symptoms  were  very  mild  and  whose  stools  were  not 
more  then  ten  a  day  the  character  of  these  being  usually  green  with 
more  or  less  mucus,  rarely  a  little  blood.  The  moderately  severe  cases 
had  usually  a  temperature  of  over  100.5  °  F.,  more  or  less  constitutional 
symptoms  and  stools  with  mucus  and  blood  averaging  ten  or  more  a 
day.  The  severe  cases  were  those  with  great  prostration,  usually  but 
not  always  a  high  temperature  and  very  numerous  stools  either  mucous 
and  bloody  or  very  thin  fluid.  As  mentioned  above  there  was  no  con- 
secutive examination  of  cases  and  only  the  severe  ones  or  those  having 
mucus  and  blood  in  the  stools  were  studied  bacteriologically.  Of  the 
mild  cases  two  were  discharged  well  and  a  third,   entirelv  over  the 


i72  Robert  W.  Hastings. 

enteric  trouble,  developed  symptoms  of  what  was  probably  central  pneu- 
monia from  which  she  finally  recovered. 

Of  the  moderately  severe  cases  one  was  discharged  well,  two  were 
improved;  one  complicated  by  tuberculous  adenitis  and  chronic  otitis 
media  was  discharged  unimproved  and  the  remaining  case  developed 
lobar  pneumonia  from  which  she  died. 

Of  the  20  severe  cases  there  were  13  who  died,  5  who  recovered  and 
2  who  were  discharged  improved,  but  ultimately  died  outside  of  the 
hospital. 

Type  of  Organism. — Of  the  28  cases,  23  were  infected  by  the  acid- 
producing  or  "Flexner-Harris"  type  of  organism,  3  with  the  true  Shiga 
type  and  in  2  cases  both  types  were  isolated.  The  small  number  of 
cases  with  the  true  Shiga  type  precludes  much  comparison.  The  3! 
cases  presented  no  marked  differences  from  the  rest  of  the  cases.  The 
2  cases  of  double  infection  were  both  severe  but  had  no  essential  dif- 
ferences in  symptoms  from  the  other  cases.  Of  these  2  cases,  one  died 
and  one  recovered.  Of  the  3  cases  of  Shiga  infection  one  was  moderate- 
ly severe  and  recovered,  one  moderately  severe  and  improved  and  one 
severe  case  died. 

Breast-fed.- — Only  2  cases  were  breast-fed  at  the  time  of  entrance. 
One,  a  boy  eleven  months  old,  well  nourished  entered  with  temperature 
104.5 °  F.,  delirious,  furred  tongue,  mild  diarrhea,  four  to  six  stools 
per  diem,  green,  with  mucus.  On  heel  of  left  foot  a  bleb  surrounded  by 
an  erysipelatous  process.  Numerous  abscesses  of  the  leg  developed  later 
which  were  opened.  The  staphylococcus  pyogenes  aureus  was  isolated 
from  these.  There  was  final  recovery.  As  the  enteric  disturbance  was 
never  severe  and  as  a  prolonged  search  of  several  hundred  colonies  re- 
vealed only  one  colony  of  the  Bacillus  dysenteries  (Flexner-Harris)  the 
relationship  as  a  causative  factor  is  problematical. 

The  other  case  was  interesting  as  to  etiology.  The  mother  stated 
that  on  account  of  a  cracked  nipple  she  had  begun  a  week  previous  to 
the  onset  to  use  a  breast  pump  of  which  little  care  had  been  taken 
and  the  milk  so  obtained  had  been  fed  to  the  child.  The  child  was  a  boy 
10  months  old,  fairly  nourished,  somewhat  rachitic,  no  teeth;  stools  8 
to  10  a  day,  green,  with  mucus  and  occasionally  streaked  with  blood ; 
considerable  tenesmus.  Temperature  99  ° — 1010  F.  Child  refused  to 
nurse,  feeding  with  dropper  was  resisted  so  as  to  exhaust  child;  after 
gavage  he  occasionally  regurgitated.  Vomiting  was  persistent  and  to- 
ward the  end  the  vomitus  contained  traces  of  blood.  On  the  day  of 
death  he  had  two  convulsions. 

Fatal  Cases.— I. — Boy,   seven   months   old.     Well   nourished,   slightly  anemic, 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  17.3 

tongue  dry,  with  white  coating;  in  collapse  on  admission.  Temperature,  104°  F. ; 
very  weak;  persistent  vomiting;  no  tenesmus.  Stools  six  to  nine  a  day,  green, 
with  mucus  and  blood.  Died  five  days  after  entrance  in  spite  of  stimulating 
treatment  and  the  injection  of  "Harris"  serum,  10  c.c,  on  each  of  three  days. 
There  was  no  change  in  the  stools  after  this,  the  temperature  rose  to  105.40  and 
the  child  died. 

II — Boy,  two  months  old,  poorly  nourished,  slight  rosary.  Few  rales  at 
back;  heart  action  weak;  peripheral  circulation  sluggish.  Child  restless.  Occa- 
sional vomiting.  Stools  six  to  ten  a  day,  green,  with  mucus;  some  tenesmus. 
Treatment,  stimulating  and  serum.  Child  lived  nine  days.  The  "Harris"  serum 
was  given  six  times,  10  c.c,  on  consecutive  days.  Child  failed  steadily.  Stools 
unchanged. 

III. — Girl,  five  months  old,  fairly  nourished.  Temperature,  1020  to  105. 6°  F. 
Pulse  weak  ;  somewhat  restless  at  times ;  prostrated  on  entrance,  with  marked 
vomiting.  Lived  forty-eight  hours.  Stools  twelve,  green,  fluid,  with  mucus,  and 
voided  with  severe  tenesmus.     Treatment,  stimulating.     No  serum. 

IV. — Girl,  colored,  three  months,  well  nourished.  Tongue  coated;  fontanel 
depressed;  pulse  weak,  intermittent;  extremities  and  skin  cold  and  clammy; 
in  stupor;  temperature,  101.50  F.  Stools  twenty  in  one  day,  thin,  faint  green 
tinge.  Face  pinched.  Died  a  few  hours  after  entrance.  Had  two  attacks  of 
convulsions.  Autopsy. — Slight  hypostatic  congestion  of  both  lungs.  Mucosa 
of  colon  slightly  injected,  no  other  gross  evidences   of  disease. 

V.— Girl,  twenty  months  old;  well  nourished.  Moribund  on  admission; 
prostrated ;  cyanosed  and  extremities  cold  ;  tenesmus ;  comatose.  Temperature, 
104.80  F.  Lived  two  hours  Treatment,  "Harris"  serum,  20  c.c.  No  response 
to   saline   infusion   nor   stimulation. 

VI. — Girl,  seven  months  old;  well  nourished.  Prostrated;  heart  sounds 
weak;  restless.  Temperature,  1010  to  1040  F.  Stools  six  to  nine,  green,  with 
mucus  and  blood.  Under  observation  Ave  days.  No  response  to  any  treat- 
ment.    No   serum. 

VII. — Boy,  thirteen  months  old;  well  nourished.  Physical  examination  nega- 
tive. Drowsy ;  slight  tenesmus ;  stools  five  to  ten  a  day,  brown,  with  mucus. 
Constant  vomiting.  Temperature,  ioo°  to  102.5 °  F-  Lived  six  days.  Treatment, 
20  c.c.  "Harris"  serum,  given  once  without  effect.  Stimulation  of  no  effect. 
Died   with   meningeal    symptoms. 

VIII. — Girl,  eighteen  months  old ;  well  nourished.  Prostrated.  Temperature, 
104.80  F.  Tenesmus  ;  stools  four,  yellow  and  green,  with  mucus.  Lived  twenty- 
eight  hours  after  entrance.  Treatment,  stimulation.  Autopsy  showed  an  early 
stage  of  follicular  ileo-colitis.     No  serum  used. 

IX. — Boy  three  years  old.  Poorly  nourished.  Physical  examination  nega- 
tive. Drowsy ;  stools  two  to  nine,  green,  with  mucus  and  streaked  with  blood. 
Treatment :  stimulation  and  saline  infusion ;  no  serum.  Case  moribund  on 
entrance. 

X. — Colored  girl,  four  months  old ;  fairly  well  nourished.  Rachitic.  Stools 
five  to  eight  a  day,  greenish-yellow,  with  mucus.  Dejections  in  several  instances 
consisted  of  purulent  material  almost  wholly  small  mononuclear  lymphocytes. 
Suffered  considerably  from  distension.  The  intestinal  trouble  had  ceased  when 
signs  of  pneumonia,  followed  by  empyema  and  purulent  pericarditis,  appeared  and 
from  this  she  died.     No  serum  had  been  used.     Duration  of  illness  fifty-five  days. 


i/4  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

XI. — Boy,  five  months  old ;  well  nourished.  Restless.  Stools  two  to  four, 
greenish-yellow,  with  mucus,  and  passed  with  tenesmus.  Gradually  fell  into 
stupor  and  died  on  the  twelfth  day.     No  serunj  used. 

XII. — Girl,  three  months  old;  well  nourished.  Prostrated  on  entrance;  some- 
what restless ;  signs  of  pneumonia  at  right  base,  posteriorly.  Autopsy  showed 
broncho-pneumonia  and  the  enteric  tract  normal.  "Harris"  serum,  two  doses, 
20  c.c.  each,  without  apparent  effect. 

XIII. — Boy,  six  months  old;  well  nourished,  slightly  anemic.  In  poor  con- 
dition on  entrance;  pulse  weak,  134.  Temperature,  103. 50  F.  Stools  eight  a  day, 
green,  with  mucus.  Under  treatment  eight  days.  '"Harris"  serum  given  twice, 
10  c.c.     No  apparent  effect. 

XIV. — Boy,  six  months  old;  well  nourished;  restless.  Marked  tenesmus. 
Stools  six  to  nine  a  day,  much  mucus  and  blood.  In  this  case  there  were 
two  distinct  recrudescences.  "Harris"  serum  was  given  for  fifteen  days  in 
10  c.c.  doses  twice  a  day  for  one  week  and  later  20  c.c.  twice  a  day  for  one 
week.  The  course  of  the  case  was  progressively  downward.  The  child  devel- 
oped purpura.  Discharged  after  being  under  observation  for  six  weeks.  Child 
died  a  week  later  at  the  Children's  Hospital. 

Two  cases  were  discharged  improved.     Both  died  later. 

Scrum  Treatment. 

Of  the  16  who  died  5  received  serum  in  addition  to  all  other  treat- 
ment ;  of  the  1 1  discharged  well,  7  had  serum ;  of  the  4  improved  2  had 
serum ;  of  the  4  unimproved  all  had  serum  before  leaving  the  hospital. 

Of  the  5  who  died  and  who  received  serum  1  received  three  doses 
of  10  c.c.  each  ;  one  five  doses  of  the  same  amount,  and  3  received  each 
one  dose  of  20  c.c. 

Of  those  discharged  unimproved  1  received  two  doses  of  10  c.c. ;  1 
three  doses  and  1  eight  doses  of  the  same  amount,  while  the  fourth  had 
20  c.c.  at  one  dose. 

Of  the  cured  who  had  serum,  3  had  two  doses  of  10  c.c. ;  1  three 
doses  and  one  nine  doses  of  the  same  amount,  while  2  had  the  larger 
close  of  20  c.c. 

One  of  the  two  discharged  improved  had  a  single  dose  of  10  c.c. 
and  the  other  had  five  doses  of  the  same  quantity. 

It  does  not  seem  that  any  positive  conclusions  can  be  drawn  from  our 
experience  with  the  serum.  We  are  confident  that  in  no  case  was  the 
child  made  worse  by  the  injection. 


A  CLINICAL  STUDY  OF  FORTY-FIVE  CASES   OF  INFEC- 
TION WITH  B.  DYSENTERIAE  (SHIGA)  OCCURRING 
AT  THE  BABIES'  HOSPITAL. 

BY  DOROTHY   M.   REED,    M.D., 
Resident   Physician  at  the   Babies'   Hospital   of  New   York. 

At  the  Babies'  Hospital,  during-  the  past  year  every  child,  passing 
mucus  in  its  stools,  has  been  carefully  watched  from  a  clinical  stand- 
point, and  if  such  stools  persisted  for  any  length  of  time,  they  have  been 
examined  bacteriologically  to  determine  the  presence  of  the  B.  dysen- 
teries (Shiga).  By  this  routine  practice  we  have  been  able  to  recog- 
nize cases  suffering  from  such  an  infection  that  would  otherwise  have 
been  overlooked.  A  positive  diagnosis  has  been  made  not  only  in  cases 
presenting  the  features  of  a  serious  dysentery,  but  also  in  others  where 
the  disease  had  reached  a  subacute  stage  prior  to  admission  to  the  hos- 
pital. The  analysis  of  the  symptoms  presented  by  these  cases  forms 
the  subject  matter  of  this  paper. 

In  collecting  this  material  the  stools  from  about  ioo  cases  showing 
intestinal  symptoms  were  examined.  This  laboratory  work  has  been 
carried  on  by  Dr.  Martha  Wollstein,  Pathologist  of  the  Babies'  Hos- 
pital. 

In  13  months  there  have  been  45  cases  in  which  the  B.  dysenteriae 
(Shiga)  has  been  isolated  from  the  stools  during  life.  During  this 
period  678  infants  under  2  years  of  age  have  been  treated  in  the  hos- 
pital wards,  and  of  these  over  half  have  been  suffering  from  some  form 
of  gastro-intestinal  disorder. 

Nineteen  cases  in  which  this  infection  occurred  were  fatal.  Twenty- 
six  cases  were  discharged  from  the  hospital,  and  in  all  but  seven  of 
these  the  intestinal  symptoms  had  disappeared.  Twenty-four  of  these 
cases  were  males,  21  were  females.     All  but  one  were  white  children. 

The  greatest  number  of  cases  were  observed  in  July,  during  which 
month,  also,  the  greatest  number  of  children  were  admitted  to  the 
hospital  and  the  proportion  of  intestinal  cases  was  highest. 


176  Dorothy  M.  Reed. 

7  cases  occurred  in  March,  1903. 

3  "                             April,    1903. 

2  '•  "               June,    1903. 

14  "  "                July.   1903. 

()  -"                             August,   1903. 

6  "                             October,    1903 

2  November,  1903. 
1  December,  1903. 
1  "                              January,    1904. 

3  "  March,    1904. 

There  did  not  seem  to  be  any  relation  between  the  season  and  the 
severity  of  the  attack.  As  large  a  proportion  of  severe  cases  occurred 
in  the  winter  months  as  in  the  summer. 

Table  Shotting  Age,  Result  and  Type  of  Infection. 

Five  were  under  3  months  of  age ;  3  died — 1  severe,  2  mild ;  2  recovered — both 
mild. 

Fifteen  were  between  3  and  6  months  of  age ;  7  died — 1  severe,  2  moderate, 
4  mild;  8  recovered — 1  moderate,  7  mild. 

Thirteen  were  between  6  and  9  months  of  age ;  4  died — 2  severe,  1  moderate, 
1  mild;  9  recovered — 3  moderate,  6  mild. 

Five  were  between  9  and  12  months  of  age;  2  died — both  severe;  3  recovered — 

1  severe,  2  moderate. 

Five  were  between  1  and  2  years  of  age ;  2  died — both  severe ;  3  recovered — 

2  severe,  1  mild. 

Two  were  over  2  years  of  age;   1   died — severe;   1   recovered — mild. 

From  this  table,  it  would  seem  that  the  age  of  the  patient  was  an 
important  factor  in  the  result;  ten  of  the  19  deaths  occurring  under  6 
months  of  age;  and  16  deaths  of  the  total  19  under  1  year  of  age. 

General  A  utritwn. — Much  more  important,  however,  in  explaining 
the  predominance  of  the  deaths  in  the  early  months  is  the  general  con- 
dition of  the  child  at  the  time  of  the  attack.  Most  of  the  children  of 
this  series  were  from  the  Xew  York  tenements,  and  were  in  bad  con- 
dition at  the  onset  of  the  disease.  The  majority  of  the  deaths  oc- 
curred in  the  youngest  infants  and  in  those  whose  general  nutrition 
was  poorest. 

Table  of  Age  and  Weight. 

Five  cases  under  3  months  old.     Weights :  sH>  6%  7,  7,  8  lbs. 
Fifteen   cases    between   3    and    6    months    old.      Weight s :    6,    7%.    7^,   8,    9, 
9,  9%,  10,  ioy2,  1 1 14,  1 1 14,  12,  12Y2.  14.34,  16  lbs. 

Thirteen  cases  between  6  and  9  months  old.     Weights  :   ~Y2,  8^,  9,  9^.   10, 

ioj4  ioy2,  10*4  1134,  12,  1314,  1414,  i$y2  ibs. 

Five  cases  between  9  and  12  months  old.  Weights:  Sl/2,  11,  n^4,  14,  i8T.<  lbs. 
Five  cases  between  1  and  2  years  old.  Weights:  141X,  16,  i8J4,  i8^4,  21  lbs. 
Two  cases  over  2  years  old.     Weights  :   16,  22lA  lbs. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  177 

Type  of  Infection. — Of  the  45  cases,  in  12  the  symptoms  were  those 
of  a  severe  infection ;  in  9  it  was  only  moderate.  The  number  and 
character  of  stools,  the  amount  of  fever  and  the  prostration,  were  con- 
sidered as  an  index  of  the  type  of  the  infection. 

In  24  cases  the  symptoms  were  very  mild ;  there  being  practically  no 
fever  or  prostration  and  the  stools  never  being  more  than  6  or  8  in 
number,  and  though  thin  with  more  or  less  mucus,  never  containing 
blood. 

Although,  as  we  have  seen,  the  prognosis  is  greatly  modified  by  the 
age  of  the  child  and  its  general  nutrition,  it  is  not  so  easy  to  bring  out 
the  relation  between  the  prognosis  and  the  severity  of  the  infection. 
Here  we  have  also  to  consider  the  individual  resistance  of  the  living 
organism  to  disease.  The  prognosis  is  also  affected  by  the  presence  of 
other  disease.  Thus  in  22  of  the  45  children,  at  the  time  of  the  dis- 
covery of  the  B.  dysenteries  in  the  dejecta,  8  were  suffering  from 
marasmus,  4  from  bronchitis,  3  from  broncho-penumonia,  2  from  lobar 
pneumonia,  2  from  acute  gastritis,  1  from  impetigo  contagiosa,  1  from 
syphilis,  and  1   from  syphilis  and  nephritis. 

Previous  Diet. — Of  the  total  number  of  cases,  25  had  been  fed  cow's 
milk,  7  condensed  milk,  6  were  breast-fed  and  2  were  taking  table 
food.  The  remaining  5  children  had  been  fed  cow's  milk  and  different 
proprietary  foods. 

Of  the. 6  breast-fed  cases,  2  were  fatal;  one  was  a  twin  4  months 
old  weighing  only  6  pounds,  who  died  in  March  with  mild  intestinal 
symptoms.  The  other  was  a  terminal  infection  of  moderate  severity 
in  a  child  5  months  old,  weighing  12  pounds  and  suffering  from  heredi- 
tary syphilis.  This  child  died  in  July.  Two  of  the  breast-fed  children 
had  severe  infections  in  hot  weather  and  recovered.  Two  breast-fed 
children,  both  well  nourished,  had  mild  infections  in  March  and  October, 
and  both  recovered. 

With  the  exception  of  the  breast-fed  cases,  most  of  the  children  had 
been  badly  fed,  and  all  the  proper  rules  in  regard  to  the  care  of  the 
food  and  general  hygiene  had  been  disregarded.  All  the  children  had 
been  given  unboiled  water  from  the  tap. 

Previous  Illness. — One  case  only  of  the  entire  series  gave  a  definite 
history  of  severe  diarrhea,  which  was  three  months  before  admission 
to  the  hospital.  The  second  attack  was,  however,  of  moderate  se- 
verity. In  2  cases  pneumonia  and  in  1  case  measles  had  directly 
preceded  the  dysentery.  In  3  cases  the  stools  were  simply  said  to  be 
"frequent"  previous  to  admission.  Four  gave  a  history  of  mild  diar- 
rhea; and  ten  gave  a  history  of  severe  diarrhea,  i.e.,  7  to  12  stools  in 


i78  Dorothy  M.  Reed. 

twenty-four  hours.  There  was  a  history  of  vomiting  as  well  as  diar- 
rhea in  12  cases.  In  I  case  there  was  no  history  in  regard  to  character 
and  number  of  stools  previous  to  admission  and  in  i  case  the  stools 
were  stated  to  be  normal. 

Fifteen  children  were  admitted  with  normal  stools,  and  did  not  show 
any  abnormal  intestinal  condition  for  from  one  week  to  two  months 
after  entrance.  These  children  were  brought  to  the  hospital  for  other 
than  intestinal  ailments. 

No  definite  information  in  any  case  could  be  obtained  from  the 
parents  in  regard  to  previous  fever,  prostration  and  other  symptoms  of 
interest. 

Of  those  admitted  with  abnormal  stools,  there  had  been  intestinal 
symptoms  for : 


3    days    or 

less 

in    7 

cases. 

5-7      "       " 

" 

"     6 

tt 

2-3  weeks    " 

" 

"     8 

" 

4-5       " 

" 

"    3 

ti 

"Always"  ' 

" 

"     1 

K 

Not  stated 

5 

" 

Food  During  Attack. — While  in  the  hospital,  the  food  in  37  cases 
was  never  changed  from  the  usual  modified  milk  suited  to  the  age  and 
general  condition  of  the  child,  as  there  did  not  seem  to  be  enough  symp- 
toms of  intestinal  trouble  to  render  a  change  of  food  necessary.  The 
digestion  of  the  upper  bowel  and  the  assimilation  of  food  in  many 
cases  did  not  seem  greatly  impaired.  The  fact  that  two-thirds  of  these 
cases  recovered  may  have  been  due  in  part  to  the  fact  that  the  digestion 
was  not  upset  by  change  of  food,  and  in  this  way  the  nutrition  of  the 
body  lowered.  In  8  cases  the  food  was  changed  to  broth,  egg  albumen 
or  gruel  in  most  instances  because  the  intestinal  symptoms  were  very 
seA'-ere.  It  seems  from  our  experience  that  while  a  fluid  diet  was  always 
indicated,  that  properly  modified  milk  was  contra-indicated  chiefly  in 
cases  where  there  was  gastritis  or  symptoms  of  involvement  of  the 
upper  bowel. 

Temperature.- — In  21  cases  of  the  series  there  was  no  rise  of  tem- 
perature over  ioo° ;  in  12  cases  (all  fatal)  the  fever  ran  from 
100  to  1060 ;  in  2  other  cases  ,  also  fatal,  there  was  pneumonia 
present  which  accounted  for  the  temperature.  In  the  10  remaining 
.cases  there  was  a  slight  irregular  rise  in  temperature,  which  in  6  cases 
was  attributed  to  other  diseases. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  179 

Character  of  Discharges. — Of  the  45  cases,  during  the  height  of  the 
disease : 

1 1  had  less  than  4-5  stools  in  24  hours. 
22,  had  from        4-7         "        24 
11  had  from         7-14        "         24 
1  had  18  "        24       " 

The  stools  in  all  cases  contained  mucus  in  varying  amount;  and 
in  seventeen  they  contained  blood.  Eight  cases  showed  blood  in  large 
amounts  and  once  there  was  quite  an  abundant  hemorrhage. 

Under  observation  for  dysentery : 

1  day   in   2  cases. 
2-7  days  in  6  cases. 
1-2  weeks   in    13   cases. 
2-4  weeks  in   13   cases. 
1-2  months   in  8  cases, 
over  2  months  in  3  cases. 

Treatment. — As  a  routine  all  cases  admitted  during  the  summer 
months  received  a  dose  of  castor  oil.  In  12  cases  other  purgatives  were 
used.  Except  for  the  initial  purgative,  we  did  not  find  t^at  drugs  in 
any  way  modified  the  course  of  the  disease,  but  often  did  harm  in  up- 
setting the  stomach.  Stimulants  were  employed,  when  indicated  by 
the  symptoms,  whiskey,  strychnia,  and,  occasionally,  digitalis  being 
used.  Rectal  irrigations  of  a  hot  saline  solution  were  used  in  5  cases, 
but  except  for  the  stimulating  effect  no  benefit  was  observed. 

SerumTreatment. — Anti-dysenteric  serum  was  given  in  14  different 
cases  in  10  c.c.  doses.  Nine  cases  received  only  one  dose ;  3  crises,  two 
doses ;  one  case,  three  doses,  and  one  case  four  doses.  The  doses 
were  usually  given  on  successive  days. 

Several  times  following  the  administration  of  the  serum  there  was 
an  apparent  decrease  in  the  number  of  stools  and  a  change  in  their 
character  for  the  next  24  or  48  hours.  In  no  case  were  we  convinced 
that  the  benefit  was  permanent.  Urticaria  twice  followed  the  use  of  the 
serum.    There  were  no  untoward  effects. 

Fatal  Cases. — As  has  been  stated  before,  19  of  the  45  cases  of  in- 
fection with  the  B.  dysenteriae  died.  In  only  13  of  the  fatal  cases, 
could  the  death  be  attributed  to  this  infection.  In  6  instances  the  dysen- 
tery infection  occurred  in  children  suffering  from  other  diseases,  and 
the  intestinal  symptoms  had  disappeared  entirely  before  the  end ;  the 
intestinal  infection  only  influencing  the  result  in  weakening  the  resist- 
ance of  the  infant.  Of  the  13  deaths  caused  directly  by  the  B.  dysen- 
terice,  8  children  showed  no  other  disease,  and  the  infection  in  all  these 


J  So  Dorothy  M.  Reed. 

was  of  a  very  severe  type.  In  5  of  the  13  cases,  the  intestinal  disease 
was  a  terminal  infection  in  children  suffering  from  other  diseases  ;  but, 
in  only  one  of  these  was  the  infection  of  a  severe  character;  3  cases 
indeed  exhibited  the  mildest  symptoms,  while  one  was  of  moderate 
severity. 

In  analyzing  the  13  deaths  due  primarily  to  the  dysentery  bacillus,  it 
is  to  be  noted  that  8  occurred  in  the  summer  months,  6  of  these  in  July. 
The  majority  of  the  severe  fatal  cases  developed  in  the  hottest  weather, 
as  was  to  be  expected. 

Of  the  13  fatal  cases : 

One  was  under  3  months  old.     Weight :  6  lbs. 

Three  were  from  3-6  months  old.     Weight :  9,   12,   i2]/2  lbs. 

Four  were   from  6-9  months  old.     Weight :   7,  jy2,  8,   10  lbs. 

Two  were  from  9-12  months  old.     Weight:   11.   14  lbs. 

Two  were  from  1-2  years  old.     Weight:  15,  16  lbs. 

One  was  2  years  old.     Weight :  16  lbs. 

Again  we  find  that  age  and  general  condition  are  the  important  factors 
in  prognosis;  10  of  the  cases  were  under  12  months  and  all  were 
poorly  nourished.  Only  3  cases  with  severe  symptoms  recovered;  2  of 
these  were  breast-fed  and  the  weight  and  general  condition  of  all  three 
were  far  above  the  average  for  hospital  patients. 

Hospital  Infection. — in  15  of  the  total  number  of  cases,  the  intestinal 
symptoms  appeared  after  the  child  had  been  in  the  hospital  one  week 
or  longer.  It  seemed  certain  that  the  infection  occurred  in  the  hos- 
pital in  at  least  5  of  these  cases.  For  instance,  a  child  two  months 
old  and  breast-fed  was  admitted  to  the  hospital  for  syphilis.  It  entered 
in  December,  and  four  months  afterwards  developed  a  mild  form  of 
dysentery.  The  stools  had  been  normal  before  this  attack.  In  such 
cases — in  consideration  of  the  age  of  the  child  on  admission,  the  previ- 
ous history,  and  the  length  of  time  under  observation  there  seemed  to 
be  no  doubt  that  the  infection  occurred  in  the  hospital.  The  other 
cases  could  be  ascribed  to  exacerbations  of  pre-existing  infection,  al- 
though in  only  one  was  there  a  definite  history  of  previous  diarrhea.  If 
it  is  possible  for  such  a  contagion  to  spread  in  the  hospital,  where  even- 
care  is  taken  to  prevent  such  a  misfortune,  and  where  practically 
"typhoid  isolation"  is  enforced,  the  danger  must  be  much  greater 
in  a  crowded  tenement  where  the  surroundings  are  unhygienic,  and 
there  is  often  gross  neglect.  In  these  cases  of  "hospital  infection" 
the  symptoms  were  very  mild  and  the  true  nature  of  the  disease  might 
have  escaped  detection  had  not  routine  bacteriological  examinations 
of  stools  containing  mucus  been  made  b\"  Dr,  Wollstein. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  181 

Lesions. — Seven  cases  in  all  came  to  autopsy.  Of  these  2  cases 
showed  practically  normal  intestines.  These  children  had  mild  infec- 
tions from  which  they  had  recovered  some  weeks  before  death,  which 
was  due  to  other  causes.  The  stools  were  normal  before  death  and  the 
B.  dysenteries  could  not  be  found  in  post-mortem  scrapings  from  the 
mucous  membrane  of  the  intestine. 

In  one  case,  that  of  an  infant  two  months  old,  there  had  been  a  severe 
infection  of  several  weeks'  duration,  which  was  the  direct  cause  of 
death.  The  autopsy  was  made  several  days  after  death,  and  the  post- 
mortem changes  were  so  marked  that  nothing  could  be  determined, 
except  that  there  was  no  ulceration  or  necrosis  of  the  intestine. 

In  2  autopsies,  the  intestines  showed  only  slight  congestion  and  some 
enlargement  of  the  solitary  follicles.  One  of  these  was  a  colored  child 
14  months  old,  markedly  rachitic,  which  had  been  sick  one  week 
with  very  severe  intestinal  symptoms.  The  death  was  apparently  due 
to  infection  with  B.  dysenterice.  The  anatomical  diagnosis,  extreme 
rachitis  and  atelectasis,  was  made  at  the  post-mortem.  The  second 
case  was  that  of  a  child  three  months  old,  suffering  from  marasmus  and 
broncho-pneumonia,  where  death  was  caused  by  a  terminal  infection 
with  the  dysentery  bacillus,  the  symptoms  being  of  the  mildest  char- 
acter. The  anatomical  diagnosis,  here,  was  broncho-pneumonia,  gen- 
eral hyperplasia  of  the  lymph  nodes  and  fatty  liver.  In  both  of  these 
cases  B.  dysenteriae  (Flexner-Harris  type)  was  isolated  from  the  post- 
mortem intestinal  scrapings. 

In  2  cases  only  were  the  intestinal  lesions  of  a  serious  nature.  One 
of  these  a  child  5  months  old  suffering  with  marasmus  had  died  with 
a  terminal  dysentery  infection.  The  intestinal  symptoms,  which  had 
lasted  about  2  weeks,  were  very  mild,  there  was  no  fever  and  the  stools 
were  only  slightly  increased  in  number  and  contained  mucus.  The 
intestines  showed  small  superficial  ulcers  throughout  the  small  intestine. 
The  Peyer's  patches  and  solitary  follicles  of  the  colon  were  enlarged 
but  not  ulcerated.  The  intestinal  coats  were  congested  in  patches.  The 
mesenteric  lymph  nodes  were  somewhat  enlarged.  There  was  also  pul- 
monary congestion  and  edema  of  the  lungs  and  fatty  liver.  In  this 
case,  also,  the  B.  dysenteriae  (Flexner-Harris  type)  was  isolated  from 
the  intestinal  mucous  membrane  at  autopsy. 

The  other  case  occurred  in  a  child  two  years  old,  in  wretched  con- 
dition, weighing  only  16  pounds,  and  just  recovering  from  measles. 
The  intestinal  symptoms  lasted  altogether  fifteen  days  and  were  most 
severe.  The  stools,  which  consisted  of  bloody  mucus,  were  from  8 
to  14  in  twenty-four  hours.     There  was  also  fever  up  to  102°,  ex- 


1 82  Dorothy  M.  Reed. 

treme  prostration  and  uncontrollable  vomiting.  Only  a  partial  autopsy 
was  permitted,  the  intestines  alone  being  examined.  The  colon  was 
mottled  red  and  gray.  The  mucosa  of  the  rectum  and  sigmoid  flexure 
was  covered  with  an  adherent  pseudo-membrane.  In  the  colon  be- 
tween the  patches  of  greenish  membrane,  were  numerous,  ulcers  ex- 
tending to  the  submucosa.  The  thickness  of  the  colon  wall  was  at  least 
three  times  greater  than  normal.  There  were  no  ulcers  in  the  small 
intestine  :  the  lymph  follicles  were  swollen,  but  only  the  Peyer's  patch 
at  the  ileo-cecal  valve  was  covered  by  pseudo-membrane.  The  appendix 
was  slightly  congested  and  covered  with  small  superficial  ulcers.  The 
mesenteric  glands  were  slightly  enlarged  and  deeply  congested.  Al- 
most pure  cultures  of  B.  dysenteriae  (  Shiga)  were  isolated  from  the 
intestinal  scrapings. 

In  the  cases  coming  to  autopsy  we  find  some  discrepancy  between  the 
clinical  picture  and  the  pathological  lesions,  although  in  this  last  case 
the  two  fitted  together  very  well.  Possibly  a  larger  series  of  post- 
mortem examinations  may  give  more  uniform  results. 

Remarks. — In  the  study  of  different  features  presented  by  this  ser- 
ies of  cases,  it  seems  possible  and  even  necessary  for  the  sake  of 
clearness  to  make  several  clinical  divisions  of  the  forms  of  intestinal 
infection  clue  to  the  B.  dysenteriae.  It  is  of  bacteriological  interest  to 
find  this  bacillus  in  the  stools  of  sick  children;  but  a  few  bad  stools  and 
the  isolation  of  a  micro-organism  do  not  establish  the  existence  of  a 
distinct  disease.  The  chief  point  of  interest  lies,  then,  in  the  ques- 
tion as  to  whether  we  have  in  children  an  acute  intestinal  infection  with 
distinct  and  constant  symptoms,  comparable  in  any  way  with  adult 
dysentery,  and  whether  the  cause  of  such  an  infection  is  a  specific  micro- 
organism. This  series  of  cases  is  interesting  in  covering  the  experience 
of  an  entire  year.,  embracing  not  only  hot  weather  cases  but  infections 
occurring  in  the  winter  months. 

In  at  least  12  of  our  cases  we  had  to  deal  with  acute  intestinal 
infection,  where  in  children  previously  considered  well,  there  was  a 
sudden  rise  in  temperature  from  100  to  1060  accompanied  by  frequent 
intestinal  discharges  and  considerable  prostration.  The  stools  ranged 
from  6  to  20  a  day.  They  were  always  thin  and  contained  mucus, 
and  usually  blood.  The  signs  of  general  toxemia  usually  ac- 
companied the  intestinal  symptoms.  The  fever,  prostration,  bad 
stools  and  toxic  symptoms  were  present  in  all  rases,  but 
usually  one  of  these  prominent  symptoms  predominated.  The  disease 
ran  a  course  of  from  one  to  three  weeks,  and.  if  terminating  favorably, 
the  recovery  was  gradual;  the   fever,  number  of  stools,  and  ereneral 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  183 

symptoms  subsiding  together.  In  acute  intestinal  indigestion,  which 
may  present  a  somewhat  similar  picture,  the  disease  is  short  and  re- 
covery often  rapid.  Three-fourths  of  these  cases  terminated  fatally 
within  ten  days  after  the  onset  of  the  first  symptoms.  The  results  with 
a  better  class  of  patients  would  undoubtedly  be  less  discouraging. 
However,  the  symptom-complex  of  an  acute,  grave  intestinal  disorder 
due  to  the  B.  dysenteriae  seems  established.  In  such  cases  we  might 
claim  that  the  clinical  and  bacteriological  entity  "'infantile  dysentery" 
had  a  right  to  recognition. 

In  a  smaller  number  of  cases  where  the  intestinal  infection  has  been 
superimposed  on  some  other  disease,  we  find  a  different  clinical  picture. 
Here  the  dysentery  may  be  regarded  as  a  terminal  infection.  There 
is  no  reason  why,  under  such  conditions,  the  intestinal  symptoms 
should  not  be  severe ;  in  those  observed  they  were  always  mild.  Hence 
we  speak  of  a  mild  infection  proving  fatal ;  as  a  child  already  enfeebled 
by  disease  cannot  withstand  what  would  otherwise  be  a  slight  diarrhea. 
In  such  cases  there  was  seen  an  increase  in  the  number  of  stools  up 
to  four  or  five  a  day,  rarely  more.  The  stools  were  thin  and  usually 
contained  mucus,  but  rarely  blood.  Sometimes  they  varied  but  little 
from  the  normal.  There  was  slight  if  any  fever,  no  increase  in  the 
prostration,  and  no  definite  toxic  symptoms.  The  infection  proved 
fatal  in  a  few  days  or  a  few  weeks. 

Of  a  similar  type,  were  the  inter-current  infections  seen  in  children 
suffering  from  other  infections  or  constitutional  diseases.  For  a  period 
of  1  to  3  weeks  the  stools  were  more  numerous,  thin  and  contained 
mucus  or  even  a  little  blocd,  but  there  was  little  or  no  fever  or  prostra- 
tion.   Such  cases  often  recovered. 

In  about  9  cases,  there  was  no  preceding  or  accompanying  disease 
and  the  symptoms  were  mild  like  those  just  described.  In  these  chil- 
dren where'  the  occasional  bad  stools  were  often  the  only  clue  to  the 
disorder,  the  condition  seemed  to  be  more  or  less  chronic.  One  such 
case  was  in  the  Hospital  in  March  and  again  in  July  and  the  B.  dysen- 
teries was  isolated  from  the  stools  on  each  admission.  There  was  no 
history  of  diarrhea  or  of  intestinal  symptoms.  This  point  is  of  in- 
terest in  connection  with  the  spreading  of  the  disease  by  cont-gion. 
Some  of  these  mild  cases  may  have  resulted  from  acute  fulminating 
cases,  such  as  described  first,  which  did  not  go  on  to  complete  cure. 
No  such  mild  case,  unassociated  with  other  disease,  proved  fatal  while 
under  observation. 

Type  of  Organism. — The  organism  isolated  from  the  stools  in  44 
caases  was  the  "Flexner-Harris"  type  of  the  B.  dysenteries  and  in  one 


184  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

case  the  true  Shiga  type  of  organism  (not  mannite- fermenting)  was 
isolated.  The  two  forms  of  the  bacillus  were  never  found  together  in 
one  case,  either  during  life  or  post-mortem.  In  3  of  the  7  autopsies 
made,  the  "Flexner-Harris"  type  of  organism  was  recovered  from 
the  intestinal  mucous  membrane  and  in  one  case  the  true  Shiga  or- 
ganism was  isolated  at  post-mortem,  it  having  been  previously  found 
in  the  stools  during  life.  In  one  case  no  culture  was  made  owing  to 
the  condition  of  the  specimen,  and  in  2  cases  the  organism  was  not 
found,  and  in  both  of  these  cases,  which  were  inter-current  infections, 
the  child  died  with  normal  stools  several  weeks  after  the  dysentery 
infection. 

Conclusions. — In  general,  from  this  study  we  believe  that  bloody 
mucus  or  much  mucus  in  the  stools,  where  there  is  no  reason  for  such 
an  appearance,  as  intussusception,  extreme  purgation,  etc.,  indicates 
infection  with  the  B.  dyscnteria-;  that  even  a  little  mucus  points  to 
such  an  infection,  if  such  stools  have  persisted  for  a  long  time.  In 
the  last  thirteen  months'  service  at  the  Babies'  Hospital  the  B.  dysen- 
teriae  has  been  isolated  from  the  stools  of  about  one-half  of  the  cases 
examined  bacteriologically  which  exhibited  symptoms  of  intestinal  in- 
flammation. 

A  certain  number  of  cases  of  infantile  diarrhea  present  a  symptom- 
complex  comparable  to  adult  dysentery  and  are  caused  by  the  B.  dysen- 
teriae.  To  this  disease  the  term  "infantile  dysentery"  may  be  properly 
applied.  In  its  severe  form  and  in  the  class  of  patients  which  make  up 
the  inmates  of  hospitals  and  other  institutions  for  infants,  the  disease 
has  a  high  mortality. 

Milder  forms  of  intestinal  inflammation  may  also  be  caused  by  the 
B.  dysentcriae.  While  these  are  not  usually  serious,  they  may  be  so  in 
very  delicate  children  where  as  a  terminal  infection  they  may  be  the 
cause  of  death. 

In  general  the  prognosis  varies  with  the  age  and  general  nutrition 
of  the  child. 

Infantile  dysentery  is  somewhat  contagious.  Even  mild  cases  may 
cause  a  spread  of  the  disease.  Hence,  disinfection  of  stools  should  be 
carefully  practiced  in  every  case. 


CLINICAL  CONCLUSIONS. 

BY   L.    EMMETT   HOLT,    M.D. 

Considerable  new  light  has  been  thrown  upon  the  subject  of  diar- 
rheal diseases  in  infants  and  young  children  by  the  clinical  investiga- 
tions of  the  summer  of  1903,  although  much  still  remains  to  be  done. 
The  summer  was  not  a  particularly  fortunate  one  for  such  an  investi- 
gation as  it  proved  to  be  an  unusually  cool  season,  and  the  diarrheal 
diseases  were  neither  so  frequent  nor  so  severe  as  in  average  years. 

Several  points  are  prominently  brought  out  by  all  the  clinical  ob- 
servations : 

1.  Infection  with  the  B.  dysenteries  occurs  under  quite  a  wide 
variety  of  conditions.  It  is  seen  in  breast-fed  infants  as  well  as  in 
those  artificially  fed. 

2.  It  occurs  (a)  as  an  acute  primary  infection  in  children  previously 
well;  (b)  as  a  subacute  infection  without  previous  acute  symptoms: 
(c)  coincident  with  or  following  other  acute  diseases  such  as  measles, 
pneumonia,  etc.;  (d)  it  is  often  seen  as  a  terminal  infection  in  children 
suffering  from  extreme  malnutrition  or  marasmus. 

3.  It  occurs  as  a  mild  intestinal  disorder  with  few  symptoms  and 
these  hardly  more  marked  than  those  belonging  to  intestinal  indiges- 
tion ;  also  with  local  symptoms  of  considerable  severity,  yet  with  very 
little  fever  or  constitutional  depression;  and  finally,  in  its  most  severe 
form,  with  both  local  and  constitutional  symptoms  of  great  severity. 

4.  It  is  not  a  disease  of  any  one  locality,  having  been  seen  with  great 
and  about  equal  frequency  in  all  the  large  cities — New  York,  Boston, 
Philadelphia  and  Baltimore — where  investigations  were  carried  on; 
the  only  variation  in  type  being  that  in  the  warmer  cities  the  propor- 
tion of  severe  acute  cases  was  rather  larger.  Nor  is  the  disease  one  of 
tenements  and  hospitals,  a  number  of  the  cases  observed  being  in  chil- 
dren living  in  the  best  surroundings,  even  in  the  country.  In  its 
prevalence,  it  appears  to  be  as  widespread  as  are  summer  diarrheal 
diseases. 

Previous  Diet. — The  clinical  reports  include  observations  upon  237 
cases.  The  previous  diet  was  studied  in  most  of  these  in  the  hope  of 
gaining  some  information  as  to  the  mode  of  entrance  of  the  organism 
into  the  body.  Of  the  cases  observed,  26  were  previously  breast-fed. 
While  in  most  of  these  the  infection  was  of  a  mild  type,  some  were 


1 86  L.  Emmett  Holt. 

severe  and  even  fatal.  That  these  attacks  were,  as  a  rule,  milder  than 
most  of  those  seen,  may  be  in  part  at  least  explained  by  the  better 
physical  condition,  and  consequently  the  greater  resistance  of  the 
breast-fed  infants.  That  so  many  attacks  were  seen  in  nursing  infants, 
shows  that  we  must  seek  for  some  other  mode  of  entrance  of  the  speci- 
fic organisms  than  with  the  milk.  Possibly  it  may  be  the  water,  al- 
though in  this  the  dysentery  bacillus  has  not  yet  been  found.  The  prac- 
tice of  boiling  water  for  the  use  of  infants  is  seldom  followed  in  the 
tenements,  and  water  in  some  form  was  given  to  almost  all  the  children. 
Xo  special  relation  of  the  infection  to  any  other  food  or  any  special 
kind  of  feeding  could  be  discovered. 

Relative  Frequency — The  relative  frequency  of  infection  with  the 
dysentery  bacillus  as  compared  with  other  diarrheal  diseases  of  in- 
fancy, cannot  be  definitely  stated  from  these  reports.  In  only  two 
groups  of  cases  were  systematic  examinations  made  of  consecutive 
■cases.  In  the  others,  the  cases  for  examination  were  more  or  less  se- 
lected, and  hence  it  is  impossible  to  draw  conclusions  from  them  as  to 
relative  frequency.  The  two  groups  of  consecutive  cases  were  those 
from  the  Yanderbilt  Clinic,  a  summer  series  reported  by  Howland  and 
La  Fetra,  and  those  from  the  Babies'  Hospital,  a  year-round  series, 
reported  by  Reed.  In  the  first  group  of  cases  the  dysentery  bacillus 
was  found  in  62  of  64  cases  examined.  They  included  every  sort  of 
intestinal  disturbance  attended  by  diarrhea.  These  figures,  however, 
do  not  prove  that  in  every  instance  this  organism  was  the  cause  of  the 
disturbance.  In  some  of  the  cases  the  number  of  dysentery  bacilli  was 
apparently  very  small ;  sometimes  only  one  or  two  colonies  were  dis- 
covered after  a  prolonged  and  careful  search.  But  their  presence  even 
in  such  small  numbers  is  interesting  as  showing  possibly  how  mild  at- 
tacks might  develop  into  severe  ones. 

In  this  connection  one  should  consider  also  Wollstein's  observations 
upon  the  stools  of  normal  children,  a  report  of  which  follows:  In  this 
it  appears  that  of  the  32  infants  whose  stools  were  studied,  in  none  was 
the  dysentery  bacillus  found,  while  of  24  other  infants  dying  from 
various  diseases,  not  intestinal,  where  cultures  were  made  from  scrap- 
ings of  the  intestinal  mucosa,  in  only  3  was  the  dysentery  bacillus  found, 
in  2  of  which  there  were  present  evidences  of  catarrhal  colitis,  while 
the  third  gave  a  history  of  previous  diarrhea. 

In  the  Babies'  Hospital  series  covering  one  year's  service,  about  one- 
half  of  all  the  cases  exhibiting  clinical  evidence  of  acute  disorders  of  the 
intestinal  tract,  showed  the  dysentery  bacillus.  These  figures  indicate 
that  this  organism  is  a  very  important  etiological  factor,  both  in  winter 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  187 

and  in  summer;  but  that  it  is  present  in  a  much  larger  proportion  of 
cases  in  summer  than  in  winter. 

Clinical  Types. — Of  the  cases  studied,  91  were  classed  as  examples 
of  severe  infection.  These  were  characterized  by  much  mucus  and 
generally  blood  in  the  stools,  usually  fever,  but  not  always  high,  and 
by  marked  general  prostration.  There  were  81  examples  of  moderately 
severe  infection,  in  which  there  was  much  mucus  and  often  blood  in 
the  stools,  some  fever  but  not  much  constitutional  depression.  There 
were  63  examples  of  mild  infection,  in  which  the  constitutional  symp- 
toms were  very  few ;  blood  was  seldom  present ;  there  was  little  or 
no  fever ;  but  the  stools  almost  always  contained  mucus.  These  fig- 
ures indicate  only  that  mild  infections  are  very  common ;  their  relative 
frequency,  however,  is  probably  much  greater  than  is  stated  here,  since 
by  several  observers  only  severe  cases  were  taken  for  examination. 

The  tvpes  of  disease  were  essentially  the  same  at  all  places  where 
the  observations  were  made.  Infection  with  the  dysentery  bacillus  was 
associated  with  almost  every  sort  of  intestinal  disturbance  accompanied 
by  diarrhea,  with,  however,  one  notable  exception,  viz.,  the  severe  acute 
intestinal  intoxication  called  "cholera  infantum,"  with  its  sudden  vio- 
lent onset,  protracted  vomiting,  high  temperature,  frequent  serous  dis- 
charges, great  prostration,  early  collapse  and  often  early  death.  There 
was  only  one  case  which  at  all  approached  this  type,  and  this  lacked 
some  of  the  essential  features.  The  infection  with  the  B.  dysenteriee 
is  associated  rather  with  the  inflammatory  forms  of  diarrhea,  and  of 
all  degrees  of  severity,  the  mildest  and  the  most  severe,  the  acute,  the 
protracted  and  subacute ;  occurring  both  as  a  primary  disease  and  a 
secondary  disease,  often  occurring  in  institutions  during  the  summer 
as  a  terminal  infection  in  infants  suffering  from  marasmus  exactly  as 
does  broncho-pneumonia  under  similar  circumstances  in  winter. 

Up  to  the  present  time  the  organism  has  not  been  found  in  cases  of 
chronic  intestinal  indigestion  in  infants  and  older  children,  even  though 
mucus  was  present  in  the  stools  in  considerable  amount.  In  this  series 
of  cases  there  were  observed  no  chronic  cases  such  as  have  been  de- 
scribed in  adults  where  bacilli  were  found  after  many  months.  The 
cases  of  long  duration  which  were  studied  in  infants,  were  usually  free 
from  bacilli  at  the  end,  death  being  due  to  progressive  marasmus. 

The  most  characteristic  clinical  type  and  the  one  with  which  the  or- 
ganism was  almost  invariably  found  associated,  was  the  acute  febrile 
form  with  stools  containing  much  mucus  and  usually  streaked  with 
blood.     For  these  cases  the  term  "infantile  dysentery"  would  seem  the 


1 88  L.  Emmett  Holt. 

only  proper  appellation.     This  type  seems  so  distinctive  that  we  may 
safely  regard  it  as  a  separate  and  distinct  disease. 

Types  of  Organism, — Of  the  237  cases  studied  clinically,  the  "Flex- 
ner-Harris"  or  '"acid"  type  of  organism  was  present  in  207,  the  true 
Shiga  in  23  and  both  organisms  were  present  in  7.  No  difference  could 
be  observed  in  the  clinical  manifestations  in  the  different  forms  of  in- 
fection. Furthermore,  the  relative  frequency  of  the  different  types  was 
nearly  the  same  in  all  places  where  the  observations  were  made. 

Whatever  may  be  said  of  the  dysentery  of  adults,  it  would  appear 
from  these  data  that  in  infants  and  young  children,  in  our  large  Eastern 
cities,  it  is  the  acid  type  of  organism  rather  than  the  true  Shiga  with 
which  we  are  chiefly  concerned. 

Mortality. — Of  the  237  cases  reported,  73  were  fatal.  This  gives 
little  idea  of  the  gravity  of  the  dysentery  infection,  since  it  is  well 
known  that  the  result  in  all  forms  of  intestinal  disease  in  infants  de- 
pends upon  nothing  so  much  as  upon  the  age  and  previous  condition 
of  the  patients.  Considerably  more  than  half  the  total  number,  139, 
were  observed  in  hospitals.  It  was  among  these  patients  also  that 
nearly  all  the  deaths  occurred,  as  might  have  been  expected.  The  poor 
general  condition  of  these  patients  and  the  late  date  of  beginning  treat- 
ment had  most  to  do  with  determining  the  results.  Again,  in  several 
it  was  noted  that  the  patients  recovered  from  the  acute  diarrhea  but 
died  subsequently  from  marasmus.  Cases  of  this  kind  were  seen  in 
almost  all  the  groups. 

In  all  acute  disorders  of  the  intestinal  tract  complex  conditions  are 
present.  No  infection  or  intoxication  can  occur  without  producing 
marked  functional  derangement  of  digestion.  In  some  cases  the  in- 
fection is  slight,  while  the  digestive  disturbance  is  severe.  The  two 
bear  a  general  but  by  no  means  a  constant  relation  to  each  other.  The 
child's  symptoms  may  be  due  almost  entirely  to  the  indigestion  and 
very  little  to  the  infection.  These  conditions  stand  in  the  way  of  suc- 
cess by  serum  treatment.  While  we  may  be  able  to  combat  the  infec- 
tion by  the  serum  it  may  be  without  any  power  to  improve  the  digestive 
disturbance.  This  also  has  a  bearing  upon  the  question  of  diet  during 
the  attacks. 

Diet  During  the  Attack, — The  necessity  of  stopping  milk  during  se- 
vere acute  infections  is  universally  agreed  upon.  There  is,  however, 
some  difference  of  opinion  in  regard  to  the  desirability  of  withholding 
milk  from  cases  of  moderate  severity,  without  temperature,  where  the 
disease  seems  to  be  limited  to  the  large  intestine.  In  these  cases  the 
symptoms  from  which  the  child  suffers  are  chiefly  those  of  wasting 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  189 

from  chronic  indigestion.  There  seems  to  be  little  doubt  from  the  ex- 
perience at  the  Babies'  Hospital  and  Vanderbilt  Clinic,  that  many  of 
these  cases  do  much  better  upon  a  properly  modified  milk  than  upon 
other  substitutes  employed,  such  as  broth,  barley  water,  albumin  water, 
etc.,  with  which  the  loss  of  weight  is  very  rapid.  In  such  cases  the  in- 
fection seems  to  play  a  minor  part  and  the  indigestion  a  major  part, 
and  therefore  one  should  not  have  his  attention  too  much  upon  the 
presence  of  infection  but  should  manage  the  child's  diet  according  to 
general  principles  as  in  other  forms  of  intestinal  indigestion. 
The  mere  presence  of  infection  with  the  B.  dysenteries  therefore  is  in 
itself  no  reason  for  withholding  milk,  and  its  intelligent  use  seems  to 
give  much  better  results  than  the  substitutes  usually  employed. 

Prevention. — The  fact  that  the  dysentery  infection  is  contagious 
seems  to  be  established,  but  how  and  to  what  degree  is  not  yet  proven. 
In  four  instances,  small  ward  epidemics  were  noted.  From  present 
experience  a  high  degree  of  contagion  does  not  seem  probable.  The 
spreading  takes  place  most  likely  through  the  discharges.  This  calls 
attention  to  the  necessity  for  disinfection  and  the  closest  attention  to 
prevent  contamination  of  food  or  water  by  persons  handling  the  child's 
napkins.  The  rule  followed  in  the  Babies'  Hospital  is  a  good  one  for 
all  institutions,  viz.,  that  the  nurse  who  is  in  charge  of  the  children's 
napkins  shall  not  at  the  same  time  have  anything  to  do  with  the  food 
or  the  feeding. 

SERUM      TREATMENT. 

In  all  there  were  83  cases  in  which  the  anti-dysenteric  serum 
was  employed ;  38  of  these  were  fatal.  On  the  whole  the  re- 
sults were  disappointing.  No  unfavorable  symptoms  followed 
its  use  in  any  case.  In  a  few  instances  eruptions,  usually  urticaria,  fol- 
lowed as  occasionally  after  diphtheria  antitoxin.  In  only  12  cases  did 
a  noteworthy  improvement  appear  to  follow  its  administration.  A 
careful  study  of  the  cases  in  which  the  serum  was  used  does  not  make 
the  results  quite  as  bad  as  at  first  appears.  Too  much  evidently  was 
expected.  The  physicians  had  in  mind  the  striking  effects  seen  after 
diphtheria  antitoxin.  These  were  observed  in  no  instance,  and  it  is 
doubtful  if  they  ever  will  be.  The  conditions  in  the  intestines  are  very 
complex  and  in  no  way  comparable  to  those  which  are  present  in  diph- 
theria. Great  disturbances  of  digestion  are  in  most  cases  present  and 
the  consequences  of  this  remain  long  after  a  specific  infection  may  have 
disappeared.  Difficulties  were  found  in  the  use  of  the  serum.  The 
quantity  in  the  strength  in  which  it  was  used  was  large.  The  mothers 
of  dispensary  patients  would  not  allow  its  use  except  in  severe  cases,  and 


190  L.  Emmett  Holt. 

often  would  not  return  for  a  second  dose.  A  brief  summary  of  the 
cases  seems  desirable. 

Freeman's  Report. — Seven  cases  treated ;  all  hospital  patients ;  in 
two  the  attack  followed  measles,  one  child  had  diphtheria  and  pneu- 
monia. In  4  cases  no  improvement.  In  3  improvement  apparently  oc- 
curred, but  2  died  later  from  marasmus  long  after  the  intestinal  symp- 
toms had  disappeared.  The  only  case  which  recovered  was  that  of  a 
nursing  child.  Full  doses  were  given ;  all  but  one  receiving  from  5 
to  10  doses  of  10  c.c.  each. 

Hou'land  and  La  Fetra's  Report. — Ten  cases  treated ;  all  dispen- 
sary patients.  Serum  used  only  in  the  severe  cases.  Two  children 
received  but  a  single  dose ;  result  unknown  as  they  did  not  return ;  2 
died,  one  moribund  when  treatment  was  begun,  the  other  recovered 
from  diarrhea,  but  died  long  after  from  marasmus ;  2  showed  decided 
improvement  after  the  serum.  In  the  other  4,  no  apparent  effects. 
Rarely  more  than  2  doses  of  10  c.c.  given. 

Amb erg's  Report. — Ten  cases  treated;  2  hospital  patients,  5  private 
practice,  3  not  stated.  Of  the  5  severe  cases,  3  ended  fatally,  1  im- 
proved and  1  recovered ;  of  the  6  moderately  severe  cases  5  recovered, 
1  improved.  Only  one  case  received  an  injection  on  the  first  day  and 
one  on  the  second  day;  3  had  been  sick  four  to  six  days  and  six  more 
than  one  week.  Six  cases  received  two  doses  and  four,  five  doses  of 
10  c.c.  each. 

W arfi eld's  Report. — Seven  cases  treated ;  2  observed  in  tenements, 
5  hospital  cases ;  4  died.  Two  were  moribund  when  the  serum  was 
given  and  one  other  had  pneumonia ;  3  apparently  benefited  by  the 
serum.  Two  patients  received  but  two  doses,  all  the  others  received 
much  larger  quantities,  one  patient  being  given  150  c.c. 

Hasting  s  Report. — Fourteen  cases  treated ;  all  hospital  patients. 
Serum  was  used  only  in  the  severe  cases.  Seven  of  these  were  fatal. 
Details  of  the  fatal  cases  only  are  given ;  one  of  these  was  moribund 
at  the  time  of  the  administration,  one  died  in  the  seventh  week  of  the 
disease;  5  were  in  poor  condition  at  the  time  of  the  attack.  No  strik- 
ing improvement  seen  in  any  case. 

Knox's  Report. — Twenty  cases  treated;  of  these  9  were  fatal. 
Three  cases  apparently  improved  from  the  serum;  in  17  apparently 
no  improvement. 

Cordes'  Report. — One  severe  case  seen  late,  no  apparent  effect. 

Reed's  Report. — Fourteen  cases ;  all  hospital  patients ;  nearly  all  se- 
vere infections.  Temporary  improvement  seen  in  several,  permanent 
improvement  in  none.     In  9  cases  only  one  10  c.c.  dose  was  given. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  191 

Such  in  brief  are  the  facts  regarding  the  use  of  the  serum  in  the 
87  cases  in  which  it  was  employed.  That  decided  improvement  ap- 
peared to  follow  its  use  in  only  12  of  the  patients  is  not  very  encour- 
aging. Several  factors  worked  against  success.  In  a  large  proportion 
of  the  cases  it  was  used  late  in  the  disease.  Again  it  was  as  a  rule 
used  only  in  the  most  severe  cases;  and,  finally,  at  the  beginning  of 
the  season  no  rules  had  been  formulated  as  to  the  size  and  frequency 
of  doses,  hence  it  is  evident  that  many  of  the  doses  were  too  small. 
Four  patients  were  moribund  at  the  time  the  serum  was  given.  Of 
the  87  cases,  67  were  hospital  patients,  and  all  familiar  with  hospitals 
for  infants  know  the  class  of  patients  referred  to. 

The  conditions  of  success,  however,  are,  first,  that  it  must  be  used 
early,  before  serious  lesions  have  developed  or  before  the  patient's 
general  nutrition  has  been  too  profoundly  impaired.  The  latter  refers 
particularly  to  cases  in  young  infants.  The  second  point  is  that  ex- 
perience shows  that  the  serum  must  be  used  in  repeated  doses,  one  or 
two  doses  given  each  day  and  continued  for  several  days  if  the  attack 
is  severe.  I  cannot  myself  feel  from  a  study  of  these  reports  and  from 
personal  observation  of  some  of  these  patients,  that  an  adequate  trial 
of  the  antidysenteric  serum  has  yet  been  made.  The  favorable  cases 
for  its  use  are  surely  not  the  subacute  infections,  where  the  symptoms 
relate  much  more  to  the  functional  disturbance  of  digestion  and  the 
resulting  impairment  of  the  child's  nutrition  than  to  the  specific  tox- 
emia of  the  dysentery  bacillus ;  nor  again  can  anything  be  expected 
from  it  in  attacks  which  develop  late  in  a  condition  of  marasmus  in 
hospital  patients.  The  promising  cases  are  rather  the  sharp 
acute  attacks  with  symptoms  of  severe  infection  occurring  in  infants 
or  older  children  with  some  powers  of  resistance ;  in  other  words,  in 
patients  where  the  real  problem  is  to  combat  the  infection,  and  not 
to  maintain  the  nutrition  of  patients,  which  even  before  the  infection 
was  a  matter  of  the  greatest  difficulty. 

Inasmuch  as  at  present  nearly  two  days  are  required  for  a  bacterio- 
logical diagnosis,  and  as  the  agglutination  reaction  is  seldom  present 
until  the  end  of  the  first  week  of  the  disease,  if  used  at  all  the  serum 
must  be  injected  on  a  clinical  diagnosis.  Its  use  would  then  be  indi- 
cated in  children  taken  with  acute  intestinal  symptoms  with  blood  and 
mucus  in  the  stools,  or  with  very  much  mucus  in  the  stools  with  fever 
and  symptoms  of  general  infection.  The  serum  surely  must  be  used 
early  and  it  must  be  given  repeatedly,  since  what  is  desired  is  to  stop  a 
process  and  not  to  neutralize  a  toxin. 

All  rules  as  to  dosage  and  frequency  must  at  present  be  tentative. 


192  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

From  the  experience  of  the  past  summer  it  would  appear  that  a  dose  of 
at  least  10  c.c.  should  be  used  daily  in  a  moderate  case;  this  being  re- 
peated two  or  three  times  daily  in  a  severe  case.  Since  we  have  no 
means  of  differentiating  clinically  the  cases  in  which  the  infection  is 
of  the  "Flexner-Harris"  and  of  the  true  Shiga  type,  it  would  seem 
best  at  present  either  to  use  a  serum  from  animals  immunized  against 
the  two  types  of  organism  or  that  from  animals  immunized  against 
the  "Flexner-Harris"  or  acid  type,  since  by  far  the  largest  number  of 
cases  are  of  this  variety.  Although  the  Shiga  serum  is  not  without  some 
effect  in  infections  with  the  "Flexner-Harris"  type  of  organism,  and 
vice  versa,  this  effect  is  much  less  than  with  the  serum  obtained  from 
inoculations  with  the  specific  organism  concerned. 

A  much  more  extended  trial  and  upon  more  carefully  selected  cases 
is  necessary  before  definite  statements  can  be  made  as  to  the  value  of 
the  anti-dvsenteric  serum. 


THE    DYSENTERY    BACILLUS    IN    RELATION     TO    THE 
NORMAL    INTESTINES     OF     INFANTS. 

BY     MARTHA     WOLLSTEIN,      M.D., 

Fellow  of  the  Rockefeller  Institute  for  Medical  Research. 

(From  the  Pathological  Laboratory  of  the  Babies'  Hospital,  May,  1904.) 

Throughout  this  paper  the  term  "Dysentery  bacillus"  is  used  to 
designate  the  bacillus  described  by  Shiga  in  1898  and  isolated  by 
him  from  cases  of  dysentery  in  Japan,  by  Kruse  in  Germany,  by  AIul- 
ler  in  Austria  and  by  Vedder  and  Duval  in  the  United  States,  and  also 
the  bacillus  found  by  Flexner  in  the  Philippines  in  1899,  later  by 
various  observers  in  the  United  States  (Duval  and  Bassett,  in  Balti- 
more, Park  in  Alt.  Desert,  Hiss,  Collins,  Goodwin  and  Wollstein  in 
New  York  City),  and  by  Jiirgens  in  Germany  in  1903.  That  both 
these  organisms  may  be  the  cause  of  dysentery  has  been  proven  by 
the  positive  agglutination  reactions  with  the  blood  of  the  patients  from 
whom  the  bacilli  were  isolated.  Shiga's  bacillus  does  not  ferment  man- 
nit ;  the  "  Flexner- Alanila"  bacillus  ferments  mannit  with  the  produc- 
tion of  acid.  The  agglutination  reactions  of  these  two  types  of  Bacil- 
lus dysenteries  are  distinct,  both  with  the  blood  of  patients  convalescent 
from  dysentery  and  with  the  serum  of  animals  immunized  to  one  type  or 
the  other.  Furthermore,  according  to  Park  and  Collins,1  the  agglutina- 
tion reactions  serve  to  subdivide  the  second  or  mannit-fermenting 
type  into  three  classes,  of  which  one  agrees  with  the  bacillus  isolated  by 
Park  in  Alt.  Desert,  another  with  the  "Harris"  culture  brought  by 
Flexner  from  Manila,  and  a  third  found  by  Collins  in  New  York  City. 

Whether  the  Shiga  type  of  dysentery  bacillus  causes  a  more  severe 
clinical  type  of  dysentery  and  a  more  intense  intestinal  lesion  than  does 
the  mannit-fermenting  type  of  the  bacillus,  future  observations  must 
determine. 

Shiga1  makes  the  statement  that  the  B.  dysenteriae  is  never  found 
in  the  dejections  of  healthy  individuals  nor  of  patients  suffering  from 

•Trans.  N.  Y.  Pathological  Society,  January,  1904. 


94 


Martha  Wollstein. 


diseases  other  than  dysentery,  and  Flexner2  was  unable  to  demonstrate 
the  organism  "in  healthy  dejecta  or  in  evacuations  of  persons  (native 
Filipinos)  suffering  from  beri-beri.*'  Under  Kruse's3  direction,  Stein 
examined  the  stools  of  thirty-three  persons  (presumably  adults),  and 
found  that  neither  in  health  nor  in  diarrhea  from  various  causes  do 
(Kruse's)  pseudo-dysentery  bacilli  occur  in  the  feces.  Drigalski4  ex- 
amined a  long  series  of  cases  of  simple  intestinal  catarrh  with  en- 
tirelv  negative  results.  Neither  dysentery  bacilli  nor  organisms  resem- 
bling them  were  found.  He  is  also  emphatic  in  his  statement  that  dysen- 
tery bacilli  are  not  found  in  healthy  subjects  nor  in  connection  with 
other  diseases,  but  only  in  patients  with  dysentery.  Knox5  mentions 
the  fact  that  Duval  and  Bassett  examined  the  normal  stools  of 
twentv-five  children,  with  negative  results.  Ford6  records  find- 
ing B.  pseudo-dysentericus  in  intestinal  contents  examined  in  the  course 
of  his  study  on  the  "Classification  and  Distribution  of  Intestinal  Bac- 
teria in  Man."  Since,  however,  his  material  was  obtained  from  au- 
topsies "regardless  of  the  morbid  conditions  present,*'  these  results  can 
have  no  bearing  upon  the  question  as  to  whether  or  not  dysentery  ba- 
cilli which  do  or  do  not  agglutinate  with  specific  anti-dysenteric  serum 
are  present  in  the  normal  intestines.  It  is  clear  that  the  finding  of  Ba- 
cillus dysenteriae  in  a  normal  stool  from  a  healthy  individual  cannot  be 
looked  upon  as  proof  positive  that  the  organism  is  a  normal  inhabitant 
of  the  intestinal  tract,  unless  the  previous  history  of  the  individual,  as 
to  exposure  to  dysentery  infection  and  the  presence  of  previous  attacks 
of  the  disease,  be  positively  known  and  such  exposure  excluded.  While 
the  bacilli  are  usually  absent  from  the  stools  or  present  in  very  small 
numbers  after  the  third  week  of  an  attack  of  dysentery,  they  may  persist 
in  the  mucosa  or  sub-mucosa  for  a  much  longer  time.  According  to 
Lentz7  the  dvsentery  bacillus  seems  occasionally  to  retain  its  viability  for 
a  very  long  time  within  the  human  body,  as  evidenced  by  cases  in  which 
relapses  occurred  many  months  after  the  primary  attack  of  dysentery. 
Drigalski*  reports  such  relapses  as  occurring  from  two  to  six  months 


'Centralbl.  f.  Bakt.,  Bd.  23,  H.  14;   Bd.  24,  H.  22,  23,  24;   Deut.  Med.  Wochens., 
3i,  Xo.  45. 

"Middleton-Goldsmith  Lecture,  1900.      (Proc.  X.  Y.  Path.  Soc.) 
3Deut.  Aerzte  Zeitung,  1902,  Xo.  2. 
4Veroff.  a.  d.  Mil.-Sanitatswesen,  H.  20,  1902. 
"Journal  of  the  Amer.  Med.  Assoc,  July  12,  1903. 
''Studies  from  the  Royal  Victoria  Hospital,  Montreal,  Vol.  I,  Xo.  5. 
7Kolle  &  Wasserman,  Handb.  d.  Pathog.  Mikroorganismen,  1903,  Vol.  2. 
sLoc.  cit. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  195 

after  the  original  onset,  in  one  case  after  the  return  of  a  soldier  from 
China  to  his  home  in  Germany.  He  looks  upon  these  cases  as  ex- 
acerbations of  an  intestinal  process  which  has  remained  without  symp- 
toms for  a  time  (as  is  characteristic  of  chronic  dysentery),  rather  than 
as  a  re-infection.  It  is  conceivable  that  any  mild  intestinal  irritation 
may  dislodge  the  bacilli,  with  or  without  a  return  of  dysenteric  symp- 
toms.   Hence  the  necessity  for  knowing  the  history  of  all  cases  studied. 

It  is  evident  that  positive  proof  as  to  the  presence  or  absence  of 
B.  dysenteriae  in  the  normal  intestinal  contents  of  infants  free  from 
gastro-intestinal  disturbance,  whose  histories  can  be  traced  from  birth, 
must  have  an  important  bearing  upon  the  question  of  the  etiological 
relationship  of  B.  dysenteriae  to  the  diarrheas  of  infancy.  For  that 
reason  the  following  study  was  undertaken1  and  conducted  in  two 
parts.  First,  children  in  the  hospital  wards,  admitted  for  diseases  other 
than  digestive,  were  selected, — only  those  being  chosen  whose  stools 
had  been  observed  and  found  normal  for  some  days.  The  bowels  hav- 
ing been  irrigated  with  saline  solution  (1 — 2  quarts),  two  drams  of 
castor  oil  were  administered  one  or  two  hours  later.2  In  some  cases 
citrate  of  magnesia  in  repeated  doses  was  used  instead  of  castor  oil. 
All  stools  passed  within  the  next  ten  hours  were  sent  immediately  to 
the  laboratory.  From  twelve  to  thirty  plates  were  poured  from  each 
stool,  and  eighteen  to  twenty-four  hours  later  tubes  of  Hiss'  semi- 
solid medium  were  inoculated  from  their  colonies.  All  non-gas-produc- 
ing bacilli  were  grown  in  litmus-milk,  in  glucose,  lactose,  saccharose 
and  mannit  broth  in  fermentation  tubes,  in  mannit  and  maltose  peptone 
agar  prepared  without  meat,  and  on  agar  slants. 

The  number  of  children  thus  treated  and  examined  was  thirty.  Two 
infants,  admitted  to  the  Hospital  at  the  age  of  one  and  two  days  re- 
spectively, were  not  dosed  with  the  laxative,  but  all  their  stools  were 
examined  during  the  time  elapsing  between  their  entrance  and  their 
death — three  and  two  days  respectively.  Thus  the  stools  from  thirty- 
two  infants  with  normal  digestion  were  examined.  In  no  instance 
was  B.  dysenteriae  found. 

The  ages  of  the  children  ranged  from  one  day  to  four  years ;  six  were 
under  two   months   old,   twenty-one   under   six  months,   twenty-eight 

lrrhe  idea  of  examining  the  stools  of  an  apparently  healthy  infant  after  the 
administration  of  a  laxative  was  first  suggested  by  Dr.  Flexner  last  summer. 
Two  children  were  then  treated  and  studied,  with  negative  results. 

2I  am  greatly  indebted  to  Dr.  Dorothy  Reed,  House  Physician  at  the  Babies'' 
Hospital,  for  the  selection  and  treatment  of  these  cases. 


196  Martha  Wollstein. 

under  one  year,  thirty-one  under  eighteen  months,  and  one  was  four 
years  old. 

The  diseases  for  which  they  were  admitted  were  as  follows  : 

Coryza   1 

Ulcerative  Stomatitis 1 

Chronic  Tonsillitis  1 

Hernia  of  Umbilical  Cord 1 

Gastritis    3 

Bronchitis    1 

Furunculosis    2 

Eczema    3 

Rachitis    2 

Chronic   Meningitis    I 

Tuberculous  Hip  Joint 1 

Malnutrition    10 

Gonorrheal  Arthritis  1 

Prematurity    1 

Well  babies   3 

Four  died :  from  prematurity,  chronic  meningitis,  marasmus,  and 
hernia  funiculi  umbilicalis  with  localized  peritonitis.  In  the  last  case 
only  was  an  autopsy  permitted,  and  the  results  of  scraping  the  intes- 
tines, post  mortem,  are  included  in  the  second  series. 

Only  one  of  these  babies  was  exclusively  breast-fed.  The  others  were 
fed  on  milk  mixtures,  variously  modified. 

The  stools,  before  the  dosage,  were  noted  as  constipated  or  normal ; 
never  was  diarrhea  present.  Following  the  lavage  and  laxative  ad- 
ministration the  stools  varied  in  number  from  one  to  five.  They  were 
always  yellow  in  color,  thin  fecal  or  formed  in  character,  sometimes 
contained  a  few  curds,  and  in  fourteen  instances  the  second  or  third  one 
showed  a  small  quantity  of  clear  mucus.  This  was  never  excessive  in 
amount,  and  no  blood  was  present  in  any  of  them.  The  two  youngest 
infants,  one  and  two  days  old.  passed  meconium  at  first  and  later  dark 
yellow  feces. 

Bacillus  coli  communis,  B.  lactis  aerogenes,  B.  alcaligenes,  Staphylo- 
coccus albus  and  Streptococci  were  found  in  varying  numbers  in  these 
stools.  But  in  no  instance  did  any  bacillus  isolated  from  them  sug- 
gest, by  its  biological  characteristics,  that  it  belonged  to  the  group  of 
B.  dysenteriae  (Shiga),  nor  did  any  one  react  with  anti-dysenteric 
serum  in  dilutions  higher  than  one  to  one  hundred.  Several  times  such 
reactions  were  obtained  with  colon  bacilli. 

The  second  part  of  the  study  included  the  examination  of  the  scrap- 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  197 

ings,  at  autopsy,  from  the  mucous  membrane  of  the  intestinal  tract  in 
children  who  died  of  diseases  other  than  intestinal.  Twenty- four  of 
these  were  studied,  varying  in  age  from  one  day  to  fourteen  months, 
including  one  still-born  infant  and  six  under  two  weeks  old  from  the 
Lying-in  Hospital.  These  very  young  infants  were  entirely  breast- 
fed. No  case  of  dysentery  was  present  in  the  hospital  at  the  time  that 
these  cases  were  observed. 

The  technique  was  as  follows :  at  the  autopsy  a  portion  of  the  je- 
junum, lower  ileum — within  six  inches  of  the  ileocecal  valve — and 
rectum — about  four  inches  from  the  anus — were  tied  off  and  then  ex- 
cised. Their  surface  was  burned  through,  the  opening  enlarged  with 
sterile  scissors,  and  the  exposed  mucosa  scraped  deeply  with  a  narrow 
platinum  spatula.  Suspensions  in  neutral  broth  were  made  from  these 
scrapings,  and  the  plates  poured  from  them  at  once.  The  aim  was  to 
obtain  that  portion  of  the  intestinal  contents  adherent  to  the  mucosa, 
rather  than  the  feces  free  in  the  lumen.  From  thirty  to  thirty-five 
plates  were  poured  from  each  case:  10-12  from  the  rectum,  the  same 
number  from  the  ileum,  and  6-10  from  the  jejunum. 

The  clinical  diagnoses  in  these  twenty- four  cases  were  as  follows : 

Septicemia    1 

Prematurity    2 

Umbilical   cord  hernia 1 

Pyemia  1 

Broncho-pneumonia     4 

Post-diphtheritic  paralysis  1 

Marasmus  8 

Congenital  syphilis  1 

Cerebral  Hemorrhage 1 

Atelectasis    3 

Stillborn  from  cord  compression 1 

24 
The  histories  state  that  the  stools  were  normal   or  constipated  in 
twenty  cases.     In  one  (congenital  syphilis)  the  stools  were  green  and 
mucous  occasionally,  but  normal  for  the  most  part.     The  other  three 
cases  are  to  be  detailed  later. 

The  intestines  at  the  autopsy  were  found  to  be  normal  in  seventeen 
instances.  In  two  a  catarrhal  colitis  was  present,  the  mucosa  of  the 
colon  being  congested  and  covered  with  a  comparatively  large  amount 
of  grayish-white  mucus,  while  the  solitary  follicles  were  distinctly  en- 
larged, but  in  no  instance  ulcerated.  These  changes  were  most  marked 
in  the  rectum  and  sigmoid  flexure,  least  marked  in  the  transverse  and 
descending  colon,  and  fairly  severe  in  the  cecum. 


198  Martha  Wollstein. 

On  microscopic  examination  the  superficial  epithelium  was  found  to 
be  lost;  the  glands  showed  many  "goblet"  cells  among  their  lining 
epithelium,  a  mass  of  mucus  and  granular  debris  lay  upon  the  free  sur- 
face of  the  glands  in  some  places,  the  blood  vessels  of  all  the  coats 
were  congested,  and  the  solitary  follicles  showed  a  simple  hyperplasia. 
No  loss  of  substance  below  the  lining  epithelium  had  occurred.  The 
sub-mucosa  was  somewhat  edematous,  but  no  cellular  infiltration  was 
present  in  this  or  in  the  muscular  coats. 

In  another  case  the  solitary  follicles  in  the  colon  and  the  Peyer's 
patches  in  the  ileum  were  all  swollen  and  congested.  No  ulceration 
was  present,  and  no  increase  in  the  amount  of  mucus  was  noted.  Fi- 
nally the  solitary  follicles  in  the  colon  were  very  slightly  enlarged  in 
three  cases,  without  any  other  change. 

Twenty-one  cases  were  entirely  negative  for  B.  dysenteriae.  In  three 
it  was  present,  once  from  the  ileum  and  rectum,  twice  from  the  rectum 
only.     The  histories  of  these  three  cases  follow  briefly : 

(1)  F.,  female,  three  months  old.  Good  family  history.  Nursed  two  weeks. 
Vomited  all  foods  tried.  Stools  "bad."  Small  emaciated  child;  lungs  negative; 
abdomen  flat.  Weight,  4  pounds  I2J4  ounces.  After  admission  she  vomited  food 
and  curds  frequently.  The  stools  were  green  with  a  little  mucus  at  first,  but 
after  four  days  became  smooth  and  normal.  She  died  one  month  after  admis- 
sion. At  autopsy  the  ileum  and  colon  were  deeply  congested  and  the  solitary 
follicles  and  Peyer's  patches  swollen  but  not  ulcerated. 

(2)  C,  male,  three  months  old,  had  cleft  palate.  Never  nursed.  Fed  store 
milk,  and  regurgitated  through  the  nose  after  each  feeding.  Did  not  gain  in 
weight.  Small,  poorly  nourished  child.  Heart  and  lungs  clear.  No  vomiting; 
normal  stools.  Weight  7  pounds  4  ounces.  In  three  weeks  he  gained  one  ounce. 
Five  days  before  death  the  stools  became  frequent — five  in  twenty- four  hours; 
green,  with  curds  and  mucus.  The  temperature  never  rose  above  101.80  F.  Died 
one  month   after  admission.     At  autopsy,   catarrhal   colitis. 

(3)  H.,  female,  three  months  old.  Was  premature  (seven  months),  kept  in 
an  incubator  two  months  and  nursed.  She  vomited  a  little  and  stools  were  green 
since.  In  the  hospital  less  than  two  days.  Vomited  curds.  Stools  green  and 
smooth,  four  in  number.     At  autopsy,  catarrhal  colitis. 

It  is  evident  that  these  three  infants  cannot  be  included  under  the 
head  of  "normal  children"  as  far  as  their  gastro-intestinal  history  is 
concerned,  although  their  digestive  disturbances  by  no  means  dom- 
inated the  clinical  picture,  and  they  were  in  no  sense  ill  with  dysentery. 
One  of  them  had  normal  stools  at  the  time  of  her  death.  They  em- 
phasize very  strongly  the  fact  that,  unless  a  child's  history  is  known 
from  birth,  the  finding  of  the  dysentery  bacillus  in  an  apparently  nor- 
mal stool  can  be  misleading  in  its  significance. 


Studies  of  the  Diarrheal  Diseases  of  Infancy.  199 

The  fact  that  two  of  these  three  positive  cases  are  the  only  ones 
in  which  an  inflammatory  intestinal  lesion  was  found,  is  of  interest 
in  this  connection.  In  the  case  C,  the  dysentery  infection  was  a  ter- 
minal one  occurring"  about  five  days  before  death.  (One  positive 
dysentery  case  was  in  the  hospital  at  the  time.) 

Case  H.  was  in  the  hospital  but  thirty-six  hours  before  her  death, 
had  had  green  and  frequent  stools  for  one  month  before  admission, 
and  probably  entered  the  hospital  with  a  dysenteric  infection  of  a 
mild  degree.  This  seems  a  more  rational  explanation  than  the  as- 
sumption that  she  acquired  the  infection  during  her  short  stay  in  the 
hospital,  when  no  other  positive  case  was  present  in  her  ward. 

F.  had  had  "bad"  stools  for  two  months  before  admission,  but  had 
recovered  from  them ;  and  throughout  three  weeks  of  her  stay  the 
stools  numbered  from  one  to  three  daily,  and  were  well  digested  and 
smooth.  This  was  probably  one  of  the  cases  in  which  the  bacilli 
remained  latent  in  the  intestinal  mucosa  after  recovery  from  an  attack 
of  dysenteric  infection. 

Bacteriological  examination:  Case  F. — In  the  plates  poured  from 
the  rectal  scrapings,  two'  non-gas-producing  organisms  were  found 
to  be  non-motile  bacilli  which  grew  in  the  fermentation  tubes  with- 
out forming  gas,  in  glucose,  saccharose,  lactose  or  mannit  broth.  Lit- 
mus-milk became  slightly  pink  in  twenty-four  hours,  but  never  coagu- 
lated; the  blue  color  (like  control)  was  restored  on  the  fourth  day. 
Acid  was  produced  in  mannit,  maltose,  dextrine  and  lactose  peptone 
agar  made  without  meat.  Saccharose  remained  unchanged.  The  ag- 
glutination reactions  were  slow  in  appearance.  Thus  in  two  hours, 
in  dilutions  of  1 -50,  agglutination  began,  and  in  sixteen  to  twenty 
hours  it  was  complete  in  dilutions  of  1-1000;  negative  in  1-1500.  For 
the  serum  with  which  the  agglutination  reactions  were  made  I  am 
•  indebted  to  Dr.  Park.  It  is  that  of  a  horse  immunized  with  mixed 
cultures  of  the  Shiga,  the  Flexner-Manila  and  the  New  York  City 
(type  A,  mannit- fermenting)  dysentery  bacilli. 

Five  c.c.  of  a  forty-eight-hour  bouillon  culture  injected  into  the  peri- 
toneal cavity  of  a  medium-sized  guinea-pig  resulted  in  death  within 
twenty-four  hours.  From  the  bloody  serum  in  the  peritoneal  cavity  the 
bacillus  was  recovered  in  pure  culture. 

A  rabbit  treated  with  dead  cultures  has  now  reached  the  point 
where  its  serum  reacts  to  the  bacillus  in  dilutions  of  1-2000,  having 
been  negative  in  1-10  before  the  injections  began.  The  Shiga  type 
of  B.  dysenterise  fails  to  react  with  the  rabbit's  serum  in  dilutions  of 


200 


Martha  Wollstein. 


i-io.  Dysentery  bacilli  of  the  mannit-fermenting  type  A  of  Dr.  Park 
(isolated  from  a  Foundling  Hospital  case)  reacts  as  high  as  1-500. 

These  experiments  are  still  being  carried  on. 

Case  C.  From  the  ileum  plates  three  non-gas-forming  organisms 
were  obtained,  and  two  from  the  rectum.  These  had  the  cultural  char- 
acteristics of  Case  F.,  but  the  agglutination  reaction  is  much  more 
rapid  in  appearance  and  is  positive  in  dilutions  of  1  to  1500,  thus 
approaching  very  closely  the  control  mannit-fermenting  type  A  which 
was  used  throughout  and  which  reacted  in  dilutions  of  1-2000  with 
the  serum  obtained  from  Dr.  Park  (Horse  221). 

Case  H.  Four  tubes  of  mannit-fermenting  B.  dysenterise  were  iso- 
lated from  the  rectum  only.  They  grew  and  reacted  like  the  bacillus 
isolated  from  Case  C. 

Using  this  mixed  serum  from  the  Board  of  Health  (Horse  221 
immunized  with  the  Shiga  and  mannit-fermenting  type  A  bacilli), 
absorption  experiments  were  made  according  to  the  technique  of  Dr. 
Park.1 

The  results  are  sriven  in  the  following  table : 


Types. 


Control  Absorption  with 


Shiga 

A.  Flexner  B 

New  York  City. 

B.  New  York  City. 

F 

H 

C 


+  500 

+ 150 

+  1,500 

— 10 

+  1,500 

— 10 

+  700 

— 10 

+ 1 ,000 

+  50 

+  1,500 

— 10 

+  1,500 

— 10 

H. 


C. 


+  150 


+  50 


Type  A. 


+  50 


Type  B. 


+  250 
+  400 
+  400 
— 10 
+  100 


H.  and  C,  therefore,  apparently  belonging  to  the  mannit-fermenting 
type  A  of  dysentery  bacilli ;  that  is,  their  specific  agglutinins  are 
similar  to  those  possessed  by  the  "Flexner-Harris"  type,  in  contra- 
distinction to  those  of  the  Mt.  Desert  type. 

The  bacillus  from  Case  F.  differs  from  either  of  the  above  types, 
and  may  be  found,  on  further  study,  to  fit  in  with  Dr.  Park's  type  C. 

From  this  study  the  following  conclusions  may  be  drawn : 

In  the  normal  stools  of  young  infants  during  life,  and  in  the  upper 
layers  of  the  normal  intestinal  mucosa  at  autopsy,  B.  dysenterise  is  not 
present. 


^roc.  of  the  N.  Y.  Patholog.  Soc,  January,  1904. 


Studies  of  the  Diarrheal  Diseases  of  Infancy. 


201 


The  accompanying  table  gives  the  facts  about  the  twenty-four  cases 
examined  at  autopsy : 


No. 

Age. 

Clinical  Diagnosis. 

Character  of              Intestines   at 
Stools.                       Autopsy. 

Bacteriology. 

i 

Stillborn 

Cord  about  neck 

Normal.       Meconi- 
um in  colon 

Jejunum,  ileum  and 
sigmoid  sterile 

2 

1  day 

Atelectasis 

Meconium 

Moderate      conges- 
tion   of   coats   of 
colon 

Gas-producing  ba- 
cilli only 

3 

2  days 

Cerebral       hemor- 
rhage 

Meconium 

Normal 

Gas-producing  ba- 
cilli only 

4 

3  days 

Prematurity 

Meconium 

Normal 

Gas-producing  ba- 
cilli and  cocci 

s 

4  days 

Hernia  of  umbilical 

Meconium  and  yel-  Normal 

Gas-producing    ba- 

cord 

low  feces 

cilli  and  cocci 

6 

9  days 

Atelectasis 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

7 

11  days 

Septicemia      (from 

Normal 

Slight   swelling    of 

Gas-producing    ba- 

pus cord) 

sol.      follicles    in 
colon 

cilli  and  cocci 

8 

11  days 

Atelectasis 

Normal 

Slight   swelling    of 
sol.     follicles    in 
colon 

Gas-producing  ba- 
cilli only 

9 

2  weeks 

Prematurity 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

IO 

17  days 

Marasmus 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

ii 

1  month 

Syphilis 

Green    and   mucusi  Normal 

Gas- producing    ba- 

alternating   with 

cilli  and  cocci 

normal 

12 

32  days 

Marasmus 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

13 

2  months 

Marasmus 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

14 

2  months 

Broncho-pneumo- 

(Only   one    day  in  Normal 

Gas-producing    ba- 

nia 

hospital.     None 
observed, 

cilli  only 

15 

2  months 

Broncho-pneumo- 
nia 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

16 

2  months 

Marasmus 

Normal 

Normal 

Gas-producing  ba- 
cilli only 

J7 

3  months 

Marasmus 

Green  with   mucus 

Congestion     of    il- 

B.    dysenteric     in 

alt.   with  normal 

eum   and    colon; 
swelling  of  P.  p. 
and  sol.  fol. 

rectum 

18 

3  months 

Marasmus  and  cleft 

Green  with  mucus. 

Catarrhal  colitis 

B.  dysenteriae  in  il- 

palate 

5  in  24  hours 

eum  and    rectum 

19 

3  months 

Marasmus  and  pre- 
maturity 

Green,  undigested 

Catarrhal  colitis 

B.  dysenteric  in 
rectum 

20 

6  months 

Broncho-pneumo- 
nia, otitis 

Constipated 

Normal 

Gas-producing  ba- 
cilli only 

21 

8  months 

Marasmus 

Yellow  and  thin        Sol.    fol.    in    colon 
slightly  swollen 

Gas-producing  ba- 
cilli only 

22 

8  months 

Broncho-pneumo- 

Normal                      Normal 

Gas-producing    ba- 

nia and  perineph- 

cilli  only 

ritic  abscess 

23 

n  months 

Pyemia 

Constipated 

Normal 

Gas-producing  ba- 
cilli, many  cocci, 
and  B.  alcalig- 
enes 

24 

14  months 

Post-diph.     paraly- 
sis 

Normal 

Noimal 

Gas-producing  ba- 
cill  and  cocci 

202  Studies  of  the  Diarrheal  Diseases  of  Infancy. 

B.  dysenteriae  may  be  present  in  the  intestinal  mucosa  in  cases  of  a 
very  mild  catarrhal  inflammation  of  the  colon,  either  as  a  terminal 
infection  or  as  the  remains  of  a  previously  active  infection,  when  the 
clinical  manifestations  do  not  warrant  the  diagnosis  of  dysentery. 

An  infant's  previous  history  is  indispensable  in  judging  of  the 
significance  of  the  presence  of  B.  dysenteriae  in  the  stool  or  the  scrapings 
from  an  apparently  normal  case. 


■    ■ 

•    •     •     .     •        ' 


COLUMBIA  UNIVERSITY 

This  book  is  due  on  the  date  indicated  below,  or  at  the 
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^^ Annex  ^« 


